The sitcom ran in first-run syndication for 10 episodes during mid-2006 on the Atlanta-area broadcast of WTBS (now WPCH-TV), along with nine other broadcast outlets across the country, as a limited run, with additional episodes to be available for national distribution on TBS in June 2007. An order of 100 episodes was later requested by TBS.
A cable record for sitcom airings was broken with 5.2 and 5.8 million for the two premiere episodes on TBS on June 6, 2007. However, the audience declined to 4.3 million as of the week ending September 30, 2007, and 2.260 and 2.099 as of May 19, 2010.
The principal cast remained the same (with the exception of Lance Gross being added), led by LaVan Davis. The original format of the series centred around C.J. (Allen Payne) and his family moving in with his Aunt Ella (Cassi Davis) and Uncle Curtis (LaVan Davis). Robinne Lee had a recurring guest stint in Season 1–2 as Malik and Jazmine's principal Nicole Jamieson, whom C.J. began dating. Rochelle Aytes originally portrayed Nicole Jamieson in the test pilot episodes as Malik's math teacher. In the test run, Ella and Curtis were originally C.J.'s parents and his name was Curtis Jr., but in its televised format, Calvin is their son and C.J. their nephew and his name was changed to Clarence. Despite his top billing, Allen Payne is not considered the main actor of the series, especially since his long absence in the fifth season. The show was recorded in front of a live studio audience but sometimes used a laugh track.
At the beginning of the fifth season, China Anne McClain (Jazmine) and Denise Burse (Claretha) were removed from the series. The characters were written out, with Jazmine going away to a school for gifted children in North Carolina and Claretha marrying a prince and moving away. In real life, McClain had gotten her own show on Disney Channel (A.N.T. Farm) and Burse left the series for undisclosed reasons. In the beginning of Season 6, both McClain and Burse returned (albeit in a recurring role). Some of the cast members of Tyler Perry's House of Payne were on The Mo'Nique Show in October 2009. Beginning with the seventh season, China Anne McClain appeared infrequently due to her work schedule for A.N.T. Farm. Denise Burse was no longer credited as a regular cast member; she appeared in a recurring role.