Popeyes was founded in Arabi, Louisiana, a suburb of New Orleans in St. Bernard Parish. It first opened its doors on June 12, 1972, as "Chicken on the Run".

By 1975, the company had been renamed Popeyes Famous Fried Chicken.

The chain expanded to Canada in 1984.

The chain opened its 500th restaurant in 1985.

By 1990, Copeland Enterprises was in default on $391 million in debts it had taken on in its 1989 purchase of Church's "Church's Chicken", and in April 1991, the company filed for bankruptcy protection.

In October 1992, the court approved a plan by a group of Copeland's creditors that resulted in the creation of America's Favorite Chicken Company, Inc. (AFC) to serve as the new parent company for Popeyes and Church's, another fast-food chain specializing in chicken.

On August 8, 2000, Popeyes announced a franchise development plan/agreement that included 35 new restaurant locations around Australia in a bid to solidify their presence within the Asia Pacific region. All were to be located in the capital city of NSW, Sydney.

AFC went public in 2001 with an initial public offering (IPO) of $142,818,479.

On December 29, 2004, "America's Favorite Chicken Company, Inc." sold Church's to Arcapita (formerly Crescent Capital Investments) retaining Popeyes.

On October 30, 2006, America's Favorite Chicken Company, Inc. "AFC" announced that Popeyes planned to introduce a trans fat-free biscuit as well as french fries containing one gram of trans fat by year-end.

In late November 2006, "America's Favorite Chicken Company, Inc." "AFC" announced the mutual termination of their licensing contract with King Features Syndicate, effectively ending their association with the Popeye characters.

On November 18, 2011, America's Favorite Chicken Company, Inc. "AFC" announced that, for the Thanksgiving holiday, Popeyes would release a Fried Turducken sandwich that would show off the first-ever Turducken patty.

On July 29, 2013, America's Favorite Chicken Company, Inc. "AFC" began offering a special entree of fried chicken strips dipped in waffle batter, which was already a proven success in some markets.

On June 17, 2014, Popeyes announced it had re-acquired full control of its seasonings, recipes, and other proprietary food preparation techniques from Diversified Foods & Seasonings, which remained under the control of Al Copeland and his estate after the creditor sale of Popeyes to AFC.

On February 21, 2017, Restaurant Brands International announced a deal to buy Popeyes for US$1.8 billion.

On March 27, 2017, the deal closed with Restaurant Brands International "RBI" purchasing Popeyes at $79 per share via Orange, Inc, an indirect subsidiary of RBI.

For a limited time only in 2017, Popeyes offered "Sweet and Crunchy" chicken, fried chicken tenders coated in shortbread cookie breading.

As of 2018, Popeyes has 3,102 restaurants worldwide.

The marketing campaign, designed by advertising agency GSD&M started on August 12, 2019, with a tweet on Popeyes' Twitter feed. The new sandwich went viral immediately and prompted responses from nearly every fast-food chain including McDonald's, Chick-Fil-A, and Wendy's.

Popeyes began selling a chicken sandwich in August 2019 to compete with Chick-fil-A's similar sandwich. The company first launched the sandwich at Long Beach restaurant Sweet Dixie Kitchen, a locally famous spot that had become known for reselling fried chicken that it had purchased at Popeyes.

On October 25, 2019, Popeyes announced that the chicken sandwich would return to locations across the US on November 3.

Popeyes opened the first store in China on May 15, 2020.

In September 2020, Popeyes' chicken sandwich went on sale in Canada.

In December 2020, Popeyes announced that it will be closing all locations in South Korea, due to poor sales partially attributed to the COVID-19 pandemic.

In March 2021, it announced plans to open stores in Mexico.

In 2021, Popeye’s introduced a flounder sandwich.