Sam Wilkes was born on July 22, 1991, and raised in Connecticut, the son of the photographer Stephen Wilkes. He took up the electric bass as a child and was drawn first to the improvisatory side of Phish and the Grateful Dead. In Los Angeles he studied R&B and funk at the USC Thornton School of Music under the keyboardist Patrice Rushen and the drummer Leon "Ndugu" Chancler, and it was at Thornton that he met the saxophonist Sam Gendel, a fellow student and the collaborator who would shape most of his recorded work.

His early Los Angeles career ran through pop and indie rock rather than jazz. With James Watson he co-founded the indie rock duo Pratley, which released a debut EP in 2011 and a self-titled full-length in 2017. In 2015 he toured with the singer Rozzi Crane, opening for Maroon 5 on the Maroon V Tour, and from 2016 he played on singles by the funk collective Scary Pockets. In 2017 he and Gendel joined the jazz-funk band Knower, first on a tour opening for the Red Hot Chili Peppers and then in several widely viewed live-recorded Knower videos. Knower's drummer, Louis Cole, played on Wilkes's solo debut and later recorded with him again.

The jazz-side work begins in 2018. Music for Saxofone & Bass Guitar, his duo record with Gendel, was recorded live to tape during casual, unannounced performances outside restaurants in Los Angeles, with both players working loops, effects and electronics. It came out on Leaving Records on June 15, 2018, and one track, "BOA," later reached a wide audience when it was used in the 2021 Netflix film Malcolm & Marie. His solo debut Wilkes followed on October 5, 2018, with Gendel, Cole and the guitarist Brian Green among the players. Pitchfork gave it 7.3 and wrote that it melts jazz structures into ambient, faintly psychedelic forms; the album opens with a reworking of John Coltrane's "Welcome." Live on the Green, a band set with Gendel, the drummer Christian Euman, the guitarists Adam Ratner and Green and the keyboardist Jacob Mann, appeared in November 2019 and includes a piece titled "The B Section of Inner Urge," after the Joe Henderson composition. In 2019 he also played bass on Chaka Khan's Hello Happiness (Island) and co-wrote its title track.

The Gendel duo kept growing. Music for Saxofone & Bass Guitar More Songs (July 21, 2021) collects nine more pieces recorded on location between 2017 and 2021, and the New York Times placed it sixth on its list of the best jazz albums of 2021, finding it at least as hypnotic as the first. In the same year Wilkes released One Theme & Subsequent Improvisation (Leaving Records, October 22, 2021), a CD whose pieces were composed spontaneously by the musicians in the room. Perform the Compositions of Sam Wilkes & Jacob Mann (September 23, 2022) is a thirteen-track set of pieces by Wilkes and Mann, and Wilkes also played electric bass on the Jacob Mann Big Band's Greatest Hits (Think! Records, 2022), on Rufus Wainwright's Rufus Does Judy at Capitol Studios (2022) and on four tracks of the vocalist Sara Gazarek's Vanity (2023). His 2023 album Driving (Wilkes Records) stepped away from the ambient jazz sound toward indie rock and chamber pop, built around acoustic guitar and his own singing.

In 2024 he released The Doober with Gendel (Leaving Records, May 1), recorded on location in Japan and Los Angeles in 2022 and 2023 and made largely of jazz-inflected reworkings of songs by Joni Mitchell, Judee Sill and Sheryl Crow. Pitchfork rated it 7.6. A trio record with the drummer Craig Weinrib and the guitarist Dylan Day followed in July, including a reading of Antonio Carlos Jobim's "How Insensitive," and the live album iiyo iiyo iiyo, recorded in Kakegawa and Tokyo, Japan, was issued in October. Wilkes also played electric bass on eight tracks of Louis Cole's orchestral album Nothing (Brainfeeder, 2024), made with the Metropole Orkest under Jules Buckley. Aquarium Drunkard's December 2024 interview introduces him as a bassist, composer, arranger and bandleader, and as one of the most sought-after musicians in the current Los Angeles jazz scene.

The next two years brought Uhlmann Johnson Wilkes (International Anthem, March 14, 2025), a trio record with the guitarist Gregory Uhlmann and the saxophonist Josh Johnson, and the solo album Public Records Performance (Wilkes Records, October 17, 2025). He also plays electric bass and sings on six tracks of the pianist Ai Kuwabara's album Flying? (July 9, 2025), a trio setting with the drummer Gene Coye. In April 2026 he released Froggy, an EP with the folk musician Sam Amidon, and Unrelated, a new duo album with Gendel. As of November 2026 he is 35 and based in Los Angeles.

Wilkes plays a Fender Precision bass, often seated, with effects and loops, and the sound he is known for is closer to ambient music than to a walking-bass rhythm section: long, patient lines under a saxophone, with the structure of jazz pieces dissolved into texture. AllMusic files him under contemporary jazz, avant-garde jazz, experimental ambient and alternative R&B, and its overview calls his solo work a fluid, meditative blend of jazz and ambient music. His background is broader than that label suggests. He grew up on the jam-band tradition of Phish and the Grateful Dead, studied funk and R&B at USC, and has spent as much of his working life in pop and indie settings as in jazz ones, from the indie rock of Pratley and the Maroon 5 tour to Chaka Khan, Maggie Rogers, Scary Pockets and his own song-based record Driving. The jazz link is documented on his own records all the same: Coltrane, Henderson and Jobim repertoire, a long partnership with the saxophonist Gendel, collaborators such as Josh Johnson and Sara Gazarek, a release on the jazz label International Anthem, and a critical reception that has placed his duo records on jazz lists in the New York Times and in Pitchfork's jazz coverage.