Sofia Kenin was born on November 14, 1998, in Moscow to Alexander and Lena Kenin. Her family moved to the United States a few months after she was born. They had previously left the Soviet Union to live in New York City in 1987 but returned to Russia for Kenin's birth so that other family members could help raise her initially. Her mother had worked as a nurse in the Soviet Union, and her parents had little money when they first moved to the United States.

Kenin began playing tennis at the age of five, drawing inspiration from her father who had played recreationally. Her parents recognized her potential and arranged for her to begin training with Rick Macci in Broward County, Florida.

Macci coached Kenin for seven years until she was twelve. He remarked, "Back then [when Kenin was five], I came right out and said Sofia was the scariest little creature I’d ever seen. It was unique: the hand-eye coordination and her ability to take the ball immediately right after the bounce. I have a lot of kids do that, but it was almost like it was baked in already, even though she was little and the racket was actually bigger than her. The only player I’ve seen like that is [former world No. 1] Martina Hingis." Her primary coach has always been her father.

Kenin had success in tennis at a young age, which garnered widespread attention in the tennis community and helped put her on the covers of tennis magazines. Kenin began playing in United States Tennis Association (USTA) girls' 10-and-under tournaments at the age of seven and became the top-ranked player in Florida in that division. She later was ranked No. 1 in the USTA national rankings for each of the 12, 14, 16, and 18-and-under divisions. Kenin had the opportunity to interact with ATP and WTA professional tennis players as a young child, including hitting with Anna Kournikova at age seven, partnering with Jim Courier against Venus Williams and Todd Martin as part of an exhibition event, and receiving a tour of the Miami Open from Kim Clijsters. She has also worked in the past with American tennis coach Nicholas James Bollettieri.

Kenin reached a career-high of No. 2 in the ITF junior rankings. She began playing in low-level Grade 4 events on the ITF Junior Circuit in 2012 at the age of 13.

After winning her first titles in both singles and doubles in 2013, she progressed to the Grade 1 level. Towards the end of the year, she made her Grade A debut at the Orange Bowl, reaching the semifinals in singles and finishing runner-up in doubles with Kaitlyn McCarthy to Tornado Alicia Black and Naiktha Bains.

Kenin made her junior Grand Slam debut in 2014, but only recorded one match win in singles while playing in the latter three events of the year. Following the US Open, Kenin represented the United States at the Junior Fed Cup alongside CiCi Bellis and Black. The team won the tournament, sweeping Slovakia 3–0 in the final. Kenin went undefeated in her five matches, all in doubles. Her next breakthrough came towards the end of the year when she won the Orange Bowl, defeating Bellis and Ingrid Neel in the last two rounds.

Kenin built on that success in 2015 by winning the USTA International Spring Championships, a Grade 1 tournament.

During the summer, she won the USTA Girls 18s National Championship as the No. 3 seed, defeating the No. 1 seed Black in the final. With the title, she earned a wild card into the main draw of the 2015 US Open.

Kenin also participated in the junior event at the US Open and finished runner-up to Dalma Gálfi, her best performance at a junior Grand Slam event. This result helped her rise to No. 2 in the world by the end of the year.

Kenin continued to play on the junior tour in 2016 while primarily playing in professional events on the ITF Women's Circuit. At the US Open, she again produced one of her best results of the year, losing in the semifinals to Viktória Kužmová after upsetting the No. 1 seed Anastasia Potapova in the previous round.

After beginning the 2017 season ranked outside the top 200, Kenin steadily rose up the WTA rankings throughout the year while playing exclusively on the professional circuit. She progressed into the top 150 in August after a string of successful results during the summer, including winning an ITF $60K tournament at Stockton and finishing runner-up at the Lexington $60K event. These ITF performances helped her win the US Open Wild Card Challenge for the second straight year.

At the 2017 US Open, Kenin advanced beyond the first round of a Grand Slam tournament for the first time, defeating compatriots Lauren Davis and Sachia Vickery before losing to the 2006 champion Maria Sharapova in the third round. These were also her first two match wins on the WTA Tour. Kenin's success at the US Open helped convince her to turn professional in September, foregoing a scholarship to attend the University of Miami. She finished the year ranked No. 108 in the world.

With her improved ranking, Kenin was able to play primarily on the WTA Tour in 2018. She began the year by reaching her first WTA quarterfinal at the Auckland Open. After losing her first-round match at the Australian Open, Kenin produced good results at both Premier Mandatory events in March. She entered the top 100 by reaching the second round of the Indian Wells Open as a qualifier. She then qualified for and reached the third round of the Miami Open, where she upset No. 11 Daria Kasatkina.

After losing all five of her WTA Tour matches on clay across main draws and qualifying, Kenin reached her first WTA semifinal at the Mallorca Open on the grass. She defeated top seed and world No. 6, Caroline Garcia, for her first career top-ten victory before losing to Tatjana Maria. Kenin closed out the grass-court season with a second-round appearance at Wimbledon, winning her debut at the event against Maria Sakkari.

Back in the United States, Kenin won another $60K title at the Berkeley Tennis Club Challenge. She reached the third round of the US Open for the second consecutive year, losing to Plíšková at the event for the second time. Kenin's best performance during the rest of the season came at the Tournoi de Québec, where she reached another semifinal. At her next tournament, she defeated world No. 10 Julia Görges at the Wuhan Open for her second top ten victory of the year. These results helped Kenin advance into the top 50 for the first time.

Kenin greatly improved in 2019, rising from outside the top 50 at the start of the year to on the cusp of the top ten by the end of the season. She began her year by winning her first WTA doubles title at the Auckland Open alongside Eugenie Bouchard. The following week, she won her maiden WTA singles title at the Hobart International without dropping a set during the event. She upset the top seed and No. 19, Caroline Garcia, in the first round before defeating Anna Karolína Schmiedlová in the final. With this success, Kenin rose to what was at the time a career-best ranking of No. 37.

Kenin also defeated the respective world No. 1 players Ashleigh Barty and Naomi Osaka at the time at each event, her first two victories over a top-ranked player. She also became the first player to defeat world No. 1 in back-to-back weeks since Lindsay Davenport in 2001.

During the Asian hard court season, Kenin won one additional title in both singles and doubles. She won her third singles title of the year at the Guangzhou International Women's Open, defeating Samantha Stosur in the final. Two weeks later, she partnered with Bethanie Mattek-Sands to win her second doubles title of the year at the China Open, a Premier Mandatory event. During the event, the pair defeated the team of Aryna Sabalenka and Elise Mertens, who were ranked No. 2 and No. 3 in the world respectively at the time. This title brought her to No. 43 in the doubles rankings. At the end of the season, Kenin qualified for the WTA Elite Trophy as the second seed, ranked No. 12 in the world. She won her opening match against compatriot Alison Riske, but lost to Karolína Muchová and did not advance out of her round-robin group. Kenin was also named the second alternate at the WTA Finals, behind Kiki Bertens. After Naomi Osaka and Bianca Andreescu both withdrew, she had the opportunity to play one match, losing to the defending champion Elina Svitolina. She finished the year ranked No. 14 in singles and No. 39 in doubles. Kenin also received the WTA Most Improved Player of the Year award for her breakthrough season, becoming the first American player to win the award since Serena Williams in 1999.

Kenin opened the 2020 seasons by playing the Premier-level events at Brisbane and Adelaide, falling in the second round of both tournaments to Osaka and compatriot Danielle Collins respectively. She also played doubles with Mattek-Sands in Adelaide, but the pair fell in the semifinals to the eventual champions Nicole Melichar and Xu Yifan. Seeded 14th at the Australian Open, Kenin recorded straight-set wins over qualifiers Martina Trevisan and compatriot Ann Li to reach the third round for the first time. She then overcame a double break deficit in the first set to defeat 2016 quarterfinalist Zhang Shuai and advance to the fourth round, where she defeated Coco Gauff to reach the quarterfinals. Kenin went on to defeat Ons Jabeur in straight sets, advancing to her first semifinal at a Grand Slam championship. She then defeated the top seed Ashleigh Barty in straight sets to reach the final, where she defeated Garbiñe Muguruza in three sets to claim the trophy. Eventually, she entered the Top ten worldwide by ranking 7th on Feb 3, 2020.

In March, Kenin won her fifth WTA singles title, defeating Anna-Lena Friedsam in the finals of the inaugural Lyon Open in Lyon, France. These results guaranteed her the No.4 rank worldwide.