In 1989, aged 16, Kwamé released his debut album, Kwamé the Boy Genius featuring a New Beginning, which he also produced with the aid of Hurby "Luv Bug" Azor. The 'A New Beginning' of the title refers to his backing band, which was unusual amongst emcees of the time. The album spawned the singles "The Man We All Know and Love" and "The Rhythm." The accompanying music videos featured a polka-dot motif in the costumes and production design. This was to become Kwamé's trademark and a hip hop fashion trend, as fans of his began wearing polka-dotted clothing. In 1990, Kwamé released his second album A Day in the Life: a Pokadelick Adventure, a concept album about a day in the life of a high school student. The album spawned the hit singles "Oneovdabigboiz" and "Ownlee Eue."
In 1992, aged 18, he released his third album, Nastee. This album marked a departure for him, discarding the polka-dots and writing more sexually charged lyrics, in contrast to his previously playful, intellectual persona. The title track was a minor hit but the album quickly fell from the charts. His fourth album, 1994's Incognito failed to chart.
In 2000, Kwamé reemerged as a music producer, sometimes working under the name K-1 Million. He has produced for many artists, such as LL Cool J, Mary J. Blige, Keyshia Cole, Missy Elliott, and Christina Aguilera. In 2004, he had a major success as the co-producer (with Eminem) of Lloyd Banks' smash hit song "On Fire." In 2005, he had more success with Will Smith's single "Switch". As a producer, Kwamé has sold over 30 million records.
In 2012, Kwamé teamed up with Vin Diesel to help score his web series The Ropes. He also formed the boutique label Make Noise, with signees including Beyond Belief, and released an instrumental album, Break Beat Diaries.
Kwamé has also written scores and original music for film and TV., including Drumline, Step Up 1 & 2, Stomp the Yard, Freedom Writers, The Comebacks, Coach Carter, and Fantastic Four and is currently producing recording artist Vivian Green 5th album entitled "V" due out early 2015. He has also joined the hip hop group the Alumni, alongside Chubb Rock, Dana Dane, Special Ed, and Monie Love.