The pilot for One on One was originally shot in 1999 and pitched to ABC, but the network passed due to declining sitcom audiences.

After ABC passed, the show was pitched to The WB, which rejected it for not being 'teen enough' following the network's rebranding, and then to Fox in 2000, which also passed.

UPN picked up the show partly because of its ties to Fox and because the cancellation of Moesha worked out in its favor; Fox Television Studios then dropped out at the last minute since the series didn't fit its financial model, prompting Paramount Television to step in as producer.

The show spawned a spin-off series called Cuts, following Flex's stepbrother Kevin Barnes running a barbershop/day spa, which premiered as a mid-season replacement in 2004-2005 and lasted two seasons before also being cancelled when UPN and The WB merged into The CW.

The series was cancelled just months before The WB and UPN merged to form The CW.

The theme song 'Living One on One' was written and performed by Shanice, who is the real-life wife of the show's star Flex Alexander, alongside Tonex, with music composed by Jonathan Wolff.

For the fifth season, the theme song was shortened and remixed by Detail and Ray J, who also joined the cast that season as the character D-Mack.

The show changed its setting from Baltimore, used for the first four seasons, to Los Angeles for its final fifth season, accompanied by a nearly complete cast overhaul including new characters D-Mack, Sara, Cash, and Lisa.