The song features guest vocals from Mase and Sean "Puff Daddy" Combs. The instrumental contains a sample of the Diana Ross song "I'm Coming Out", including backing vocals which repeat the title of that song. The refrain of the song was sung by Kelly Price. Based on airplay and chart success the song is considered one of the most popular singles in hip hop history.
"Mo Money Mo Problems" was able to top the Billboard Hot 100 for two weeks, giving Biggie his second number one hit in the US. The song hit number one after he had died. It was preceded by "I'll Be Missing You" by Puff Daddy featuring 112 and Faith Evans (meaning that Puff Daddy spent 13 weeks in a row at the top of the Hot 100) and was succeeded by "Honey" by Mariah Carey, which was also co-produced by Puff Daddy. "Mo Money Mo Problems" also reached number six on the UK Singles Chart.
The video directed by Hype Williams featured Mase and Combs in futuristic locations designed by Ron Norsworthy, including a tunnel lined with fluorescent lamps and a stark white chamber with pressurized air blowing out of the floor, allowing the two to float in midair. This video is also famous for the red shiny jackets that are worn by Combs and Mase. The "air chamber" also had a video screen showing, at first, images of Kelly Price lip-synching to the sample of Diana Ross' voice and singing the song's chorus. During the final verse, which the Notorious B.I.G. performed, Mase and Puffy looked on as the video screen showed archival footage of B.I.G. performing, it ran at a speed so that the footage seemed to sync with B.I.G.'s vocals; since the rapper had died just prior to the release of Life After Death, and well before the filming of the video, this was the only way to have him appear in the video. The video features appearances from Sheek Louch of The LOX, Riddick Bowe, Stevie J, and Nashiem Myrick.
The video also has a short story, which is about how Combs was competing in a golf tournament and gained help from the spirit of The Notorious B.I.G, who helps him win the tournament. This was a reaction to the newly popular success of Tiger Woods.
MuchMoreMusic ranked "Mo Money Mo Problems" number 31 on Listed's "40 Most Memorable Videos Pt. 1 & 2" for its flashy wardrobe, and use of syncing old footage with the lyrics. VH1 ranked the song number 63 as one of the "100 Greatest Songs of the 90s".