Anna's paternal grandfather, A Wong Wong, was a merchant who owned two stores in Michigan Hills, a gold-mining area in Placer County. He had come from Chang On, a village near Taishan, Guangdong Province, China, in 1853.

Wong's parents were second-generation Chinese Americans; her maternal and paternal grandparents had resided in the U.S. since at least 1855.

Anna's father returned to the U.S. in the late 1890s and in 1901, while continuing to support his family in China, he married a second wife, Anna May's mother. Anna May's older sister Lew Ying (Lulu) was born in late 1902, and Anna May in 1905, followed by five more children.

Anna May Wong was born Wong Liu Tsong (Liu Tsong literally meaning "willow frost") on January 3, 1905, on Flower Street in Los Angeles, one block north of Chinatown, in an integrated community of Chinese, Irish, German and Japanese residents.

In 1910, the family moved to a neighborhood on Figueroa Street where they were the only Chinese people on their block, living alongside mostly Mexican and Eastern European families. The two hills separating their new home from Chinatown helped Wong to assimilate into American culture.

By the age of 11, Wong had come up with her stage name of Anna May Wong, formed by joining both her English and family names.

Wong was working at Hollywood's Ville de Paris department store when Metro Pictures needed 300 female extras to appear in Alla Nazimova's film The Red Lantern (1919). Without her father's knowledge, a friend of his with movie connections helped her land an uncredited role as an extra carrying a lantern.

Wong worked steadily for the next two years as an extra in various movies, including Priscilla Dean and Colleen Moore pictures. While still a student, Wong came down with an illness identified as St. Vitus's Dance which caused her to miss months of school. She was on the verge of emotional collapse when her father took her to a practitioner of traditional Chinese medicine. The treatments proved successful, though Wong later claimed this had more to do with her dislike of the methods.

Finding it difficult to keep up with both her schoolwork and her passion, Wong dropped out of Los Angeles High School in 1921 to pursue a full-time acting career.

In 1921, Wong received her first screen credit for Bits of Life, the first anthology film, in which she played the wife of Lon Chaney's character, Toy Ling, in a segment entitled "Hop".

At the age of 17, Wong played her first leading role, in the early Metro two-color Technicolor movie The Toll of the Sea. Written by Frances Marion, the story was based loosely on Madama Butterfly. Variety magazine singled Wong out for praise, noting her "extraordinarily fine" acting.

At the age of 19, Wong was cast in a supporting role as a scheming Mongol slave in the 1924 Douglas Fairbanks picture The Thief of Bagdad. Playing a stereotypical "Dragon Lady" role, her brief appearances on-screen caught the attention of audiences and critics alike.

In March 1924, planning to make films about Chinese myths, she signed a deal creating Anna May Wong Productions; when her business partner was found to be engaging in dishonest practices, Wong brought a lawsuit against him and the company was dissolved.

Wong continued to be offered exotic supporting roles that followed the rising "vamp" stereotype in cinema. She played indigenous native girls in two 1924 films. Filmed on location in the Territory of Alaska she portrayed an Eskimo in The Alaskan.

Wong returned to Los Angeles to perform the part of Princess Tiger Lily in Peter Pan. Both films were shot by cinematographer James Wong Howe but Peter Pan was more successful; the hit of the Christmas season.

Wong was singled out for critical praise in a manipulative Oriental vamp role in the film Forty Winks.

In early 1925 Wong joined a group of serial stars on a tour of the vaudeville circuits; when the tour proved to be a failure, Wong and the rest of the group returned to Hollywood.

In 1926, Wong put the first rivet into the structure of Grauman's Chinese Theatre when she joined Norma Talmadge for its groundbreaking ceremony, although she was not invited to leave her hand- and foot-prints in cement.

In Mr. Wu (1927) Wong played a supporting role as increasing censorship against mixed-race onscreen couples cost her the lead. In The Crimson City, released the following year, this happened again.

Wong starred in The Silk Bouquet. Re-titled The Dragon Horse in 1927, the film was one of the first U.S. films to be produced with Chinese backing, provided by San Francisco's Chinese Six Companies. The story was set in China during the Ming Dynasty and featured Asian actors playing the Asian roles.

Wong continued to be assigned supporting roles. Hollywood's Asian female characters tended toward two stereotypical poles: the naïve and self-sacrificing "Butterfly" and the sly and deceitful "Dragon Lady". In Old San Francisco (1927), directed by Alan Crosland for Warner Brothers, Wong played a "Dragon Lady", a gangster's daughter.

Tired of being both typecast and being passed over for lead Asian character roles in favor of non-Asian actresses, Wong left Hollywood in 1928 for Europe.

In Europe, Wong became a sensation, starring in notable films such as Schmutziges Geld (aka Song and Show Life, 1928) and Großstadtschmetterling (Pavement Butterfly).

In Vienna, she played the title role in the operetta Tschun Tschi in fluent German.

Wong made her last silent film, Piccadilly, in 1929, the first of five English films in which she had a starring role. The film caused a sensation in the UK.

While in Germany, Wong became an inseparable friend of the director Leni Riefenstahl. Her close friendships with several women throughout her life, including Marlene Dietrich and Cecil Cunningham, led to rumors of lesbianism which damaged her public reputation.

Wong's first talkie was The Flame of Love (1930), which she recorded in French, English, and German. Though Wong's performance – particularly her handling of the three languages – was lauded, all three versions of the film received negative reviews.

During the 1930s, American studios were looking for fresh European talent. Ironically, Wong caught their eye, and she was offered a contract with Paramount Studios in 1930.

In November 1930, Wong's mother was struck and killed by an automobile in front of the Figueroa Street house.

In the 1930s, the popularity of Pearl Buck's novels, especially The Good Earth, as well as growing American sympathy for China in its struggles with Japanese imperialism, opened up opportunities for more positive Chinese roles in U.S. films.

With the promise of appearing in a Josef von Sternberg film, Wong accepted another stereotypical role – the title character of Fu Manchu's vengeful daughter in Daughter of the Dragon (1931).

Wong began using her newfound celebrity to make political statements: late in 1931, for example, she wrote a harsh criticism of the Mukden Incident and Japan's subsequent invasion of Manchuria.

Wong appeared alongside Marlene Dietrich as a self-sacrificing courtesan in Sternberg's Shanghai Express.

Peking University awarded the actress an honorary doctorate in 1932.

After her success in Europe and a prominent role in Shanghai Express, Wong's Hollywood career returned to its old pattern. Because of the Hays Code's anti-miscegenation rules, she was passed over for the leading female role in The Son-Daughter in favor of Helen Hayes.

Wong also became more outspoken in her advocacy for Chinese American causes and for better film roles. In a 1933 interview for Film Weekly entitled "I Protest", Wong criticized the negative stereotyping in Daughter of the Dragon, saying, "Why is it that the screen Chinese is always the villain? And so crude a villain – murderous, treacherous, a snake in the grass! We are not like that. How could we be, with a civilization that is so many times older than the West?".

The family remained at the house until 1934 when Wong's father returned to his hometown in China with Anna May's younger brothers and sister.

In 1934, the Mayfair Mannequin Society of New York voted her "The World's best-dressed woman".

Wong's film Java Head (1934), though generally considered a minor effort, was the only film in which Wong kissed the lead male character, her white husband in the film. Wong's biographer, Graham Russell Hodges, commented that this may be why the film remained one of Wong's personal favorites.

Wong returned to Britain, where she stayed for nearly three years. In addition to appearing in four films, she toured Scotland and Ireland as part of a vaudeville show. She also appeared in the King George Silver Jubilee program in 1935.

Wong returned to the U.S. in June 1935 with the goal of obtaining the role of O-lan, the lead female character in MGM's film version of The Good Earth. Since its publication in 1931, Wong had made known her desire to play O-lan in a film version of the book; and as early as 1933, Los Angeles newspapers were touting Wong as the best choice for the part.

Embarking in January 1936, Wong chronicled her experiences in a series of articles printed in U.S. newspapers such as the New York Herald Tribune, the Los Angeles Examiner, the Los Angeles Times, and Photoplay.

In contrast to the usual official Chinese condemnation of Wong's film roles, the Chinese consul to Los Angeles gave his approval to the final scripts of two of these films, Daughter of Shanghai (1937) and King of Chinatown (1939).

In October 1937, the press carried rumors that Wong had plans to marry her male co-star in this film, childhood friend and Korean-American actor Philip Ahn. Wong replied, "It would be like marrying my brother."

Bosley Crowther was not so kind to Dangerous to Know (1938), which he called a "second-rate melodrama, hardly worthy of the talents of its generally capable cast".

In 1938 Look magazine named her "The World's most beautiful Chinese girl".

In 1938, having auctioned off her movie costumes and donated the money to Chinese aid, the Chinese Benevolent Association of California honored Wong for her work in support of Chinese refugees.

Being sick of the negative typecasting that had enveloped her throughout her American career, Wong visited Australia for more than three months in 1939. There she was the star attraction in a vaudeville show entitled 'Highlights from Hollywood' at the Tivoli Theatre in Melbourne.

Wong performed on radio several times, including a 1939 role as "Peony" in Pearl Buck's The Patriot on Orson Welles' The Campbell Playhouse.

Between 1939 and 1942, Wong made few films, instead engaging in events and appearances in support of the Chinese struggle against Japan.

Wong attended several socialite events at the Mission Inn in Riverside, California, in 1941.

The proceeds from the preface that she wrote in 1942 to a cookbook entitled New Chinese Recipes, one of the first Chinese cookbooks, we're also dedicated to United China Relief.

Wong starred in Bombs over Burma (1942) and Lady from Chungking (1942), both anti-Japanese propaganda made by the poverty row studio Producers Releasing Corporation. She donated her salary for both films to United China Relief.

Later in life, Wong invested in real estate and owned a number of properties in Hollywood. She converted her home on San Vicente Boulevard in Santa Monica into four apartments that she called "Moongate Apartments". She served as the apartment house manager from the late 1940s until 1956, when she moved in with her brother Richard on 21st Place in Santa Monica.

After a six-year absence, Wong returned to film the same year with a small role in a B movie called Impact.

In 1949, Wong's father died in Los Angeles at the age of 91.

From August 27 to November 21, 1951, Wong starred in a detective series that was written specifically for her, the DuMont Television Network series The Gallery of Madame Liu-Tsong, in which she played the title role that used her birth name.

A Democrat, Wong was supportive of Adlai Stevenson's campaign during the 1952 presidential election.

Wong's health began to deteriorate. In late 1953 she suffered an internal hemorrhage, which her brother attributed to the onset of menopause, her continued heavy drinking, and financial worries.

Wong also did guest spots on television series such as Adventures in Paradise, The Barbara Stanwyck Show, and The Life and Legend of Wyatt Earp.

In 1956, Wong hosted one of the first U.S. documentaries on China narrated entirely by a Chinese American. Broadcast on the ABC travel series Bold Journey, the program consisted of film footage from her 1936 trip to China.

For her contribution to the film industry, Anna May Wong received a star at 1708 Vine Street on the inauguration of the Hollywood Walk of Fame in 1960.

In 1960, Wong returned to film in Portrait in Black, starring Lana Turner. She still found herself stereotyped, with one press release explaining her long absence from films with a supposed proverb, which was claimed to have been passed down to Wong by her father: "Don't be photographed too much or you'll lose your soul", a quote that would be inserted into many of her obituaries.

On February 3, 1961, at the age of 56, Anna died of a heart attack as she slept at home in Santa Monica, two days after her final screen performance on television's The Barbara Stanwyck Show.

In 2016, the novelist Peter Ho Davies published The Fortunes, a saga of Chinese-American experiences centered around four characters, one of whom is a fictionalized Anna May Wong, imagined from childhood until her death. In a conversation published in the 2017 paperback edition, Davies described his novel as an exploration of the Chinese-American quest for authenticity – a third way of being Chinese-American – with Anna May Wong representing an iconic example of that struggle.

On January 22, 2020, a Google Doodle celebrated Wong, commemorating the 97th anniversary of the day The Toll of the Sea went into general release.