In April 2005, Moby stated that "South Side" was inspired by his visits to Chicago and his love for its house music scene, but that its lyrics are intended to be unsettling and imply a connection between getting used to loud music as part of clubbing, and desensitization to violence.

"[3] During the recording sessions for Moby's fifth studio album Play, Gwen Stefani, lead singer of the rock band No Doubt, offered to perform guest vocals for "South Side".

[3] Around the time of the song's recording, No Doubt had recently achieved substantial commercial success with their 1995 album Tragic Kingdom, and Moby reflected that he "couldn't figure out why she'd want to go into the studio with me.

[3] It was first sent to modern rock and adult contemporary radio in October 2000 and was aired by top 40 stations the following month.

In the United States, the song debuted at number 94 on the Billboard Hot 100 chart dated December 2, 2000.

Other elements observed in the video include Moby expressing discomfort for the fake gold insert used over his teeth.

Stefani is shown in one scene in front of the neon sign with her name wielding three-inch fingernails.

Coincidentally, Stefani was also a featured singer in the winner for Best Female Video, "Let Me Blow Ya Mind" by Eve.