The label was established in 1993 as a joint venture with Columbia Records; its first act was female R&B group Xscape, whose debut album was released in the fall of the same year and went platinum—as did their second and third albums, released in 1995 and 1998 respectively. In 1994, the label released the debut album of Da Brat, who immediately became the first solo female emcee to be certified for platinum album sales. In 1996, Kandi Burruss (of Xscape) brought the singing group Jagged Edge to the attention of So So Def, with its 1998 debut A Jagged Era. In 2000, So So Def released the debut album of Bow Wow, which was certified double platinum.

Other acts on the label have included: Manish Man, Dem Franchise Boyz, T Waters, SunN.Y., Maestro Harrell, The Ghost Town DJs, INOJ, The Kid Slim, Young Capone, J-Kwon, Lathun, Trina Broussard, R.O.C., Short Dawg, Anthony Hamilton, and Sponge (R&B singer).

In 2002, So So Def's distribution deal with Columbia Records ended. The following year, Dupri moved So So Def to Arista Records, where he was appointed president of Black Music. While many of So So Def's acts moved with the label to Arista, Bow Wow and Jagged Edge were forced to remain at Columbia, due to their contracts having been with that company primarily. In 2004, So So Def was shifted from Arista to Zomba Music Group because of the Sony-BMG merger.

In 2005, Dupri was appointed Executive Vice President of Urban Music at Virgin Records, causing So So Def to move again, this time over to Virgin and EMI—resulting in the loss of acts such as Bone Crusher and the YoungBloodZ. So So Def, meanwhile, was able to retain J-Kwon and Anthony Hamilton, despite their still being signed to Zomba. In 2006, Dupri had a falling out with Virgin, resulting in his leaving his post at the company. Intermittent, he was appointed President of urban music at Universal Music Group's Island Records, resulting in So So Def once again making a move to UMG's The Island Def Jam Music Group, where it currently operates.