Deen was born Paula Ann Hiers in Albany, Georgia,[2] the daughter of Corrie A. Hiers (née Paul) and Earl Wayne Hiers, Sr.[4][5] She grew up Baptist, and is still deeply devoted to her faith.[6] Her parents died before she was 23, and an early marriage ended in divorce. In her 20s, Deen suffered from panic attacks and agoraphobia. She then focused on cooking for her family as something she could do without leaving her house.[7] Her grandmother Irene Paul had taught her the hand-me-down art of Southern cooking;[8] one of the only places she felt safe was at her own stove, making thousands of pots of chicken and dumplings.[9] She later moved to Savannah, Georgia, with her sons. In 1989, she divorced her husband, Jimmy Deen, to whom she had been married since 1965.[10] She was left with only $200[2] and money was tight raising both her kids and her younger brother, Earl ("Bubba"). She tried hanging wallpaper, working as a bank teller, and selling real estate and insurance.[9] She then started a catering service,[11] making sandwiches and meals, which her sons Jamie and Bobby delivered. Deen's home business, The Bag Lady, soon outgrew her kitchen. She first moved into the Best Western on Savannah's southside on Abercorn Street in 1991 with a restaurant called The Lady. In January 1996,[12] Deen opened her restaurant, The Lady & Sons, in downtown Savannah, on West Congress Street. Within a few years, the restaurant moved to the old White Hardware building on Whitaker. USA Today named The Lady & Sons the "International Meal of the Year" in 1999. The specialty is a buffet of Southern "comfort foods".[13] Every buffet meal includes a salad bar and one dessert. Her sons are also involved in managing the restaurant, which is popular with tourists visiting Savannah.[14] Deen owned four casino buffets; they were at Harrah's Casino Tunica in Mississippi, Harrah's Cherokee casino in North Carolina, Horseshoe Southern Indiana, and Harrah's Joliet in Illinois. They were rebranded in 2013 shortly after Deen was removed from the Food Network.[15]

In September 2009, Deen announced a new dessert line to be sold at Walmart including signature pies Apple Crunch Top, Dark Rum Pecan, Old Fashioned Fudge and St. Louis style Gooey Butter Cake bars.[16] In addition to these, Deen co-owned Uncle Bubba's Oyster House in Savannah Georgia. It underwent an "abrupt closure" on April 4, 2014[17] with a spokesperson saying that there were discussions about development of the waterfront property.[18] The property will reopen in June 2017 as Paula Deen’s Creek House and will be a joint venture of Deen and her two sons.[19] On April 27, 2015, Deen opened Paula Deen's Family Kitchen, her new restaurant and retail concept, in Pigeon Forge, Tennessee.[20] On January 25, 2016, the city of Myrtle Beach, South Carolina received an application for a building permit for a two-story Paula Deen's Family Kitchen, to replace the 20-year-old Carlos 'n Charlie's at Broadway at the Beach.[21] In June 2017, Paula Deen opened her Myrtle Beach location. In November 2017, Deen announced that two new Paula Deen restaurants would open in Texas. One location in Dallas is set to open in Spring 2018 and the San Antonio location will open 6–8 weeks later.