Wise signed with the English record label Tri Angle to release his debut extended play (EP), Blisters (2016).

He entered a joint venture with Secretly Canadian to release his debut studio album, soil (2018), which was met with critical acclaim.

When he was 11 years old his mother asked him if he wanted to audition for the Maryland State Boychoir and, ignoring his refusal, she signed him up anyway and he ended up loving it.

After this, Wise decided that he wanted to become a world-class performer and he started taking vocal lessons to become a classically trained opera singer.

[8][9][10] Wise began work on his debut studio album Soil in 2017 with producers including Clams Casino, Katie Gately, and Adele collaborator Paul Epworth.

[11][12][13] AllMusic observed that serpentwithfeet brought avant-garde elements into his usual mix of R&B, gospel and classical sounds to create a sense of aching sadness.

[16] On the Brockhampton album Iridescence (2018), Serpentwithfeet features on the song "Tonya", which was first performed live on The Tonight Show Starring Jimmy Fallon.

[24] In January 2021, Serpentwithfeet announced his second studio album Deacon, and release the lead single "Fellowship", co-produced with Sampha and Lil Silva.