Talmage Holt Farlow was born on June 7, 1921, in Greensboro, North Carolina, the son of a textile-plant worker, and he was expected to follow his father into the mills. Instead he spent his evenings with radio broadcasts of the dance bands, among them the orchestras of Count Basie, Benny Goodman and Coleman Hawkins. He took up the guitar at 22, teaching himself, and worked out his chord-melody approach on a mandolin strung like a ukulele. His only formal training was as an apprentice sign painter, a job he took on the night shift so that he could listen to big-band radio at the shop. Hearing Charlie Christian with the Goodman band inspired his playing, and after working in dance and society bands in the South he moved to New York in the late 1940s.

In New York he worked with vibraphonists, first in Dardanelle's trio and then in Marjorie Hyams's group, which shared a bill at the Three Deuces with a Charlie Parker quintet, and he also played in clarinetist Buddy DeFranco's band. He lived in an apartment house on West 93rd Street that doubled as a gathering place for guitarists, among them Jimmy Raney and Sal Salvador, with Johnny Smith dropping by for the jam sessions. At the end of 1949 he joined the Red Norvo Trio, replacing Mundell Lowe in the unusual vibraphone, guitar and bass lineup. He struggled at first with Norvo's fast tempos and then became one of the quickest guitarists in jazz. With Charles Mingus on bass in 1950 and 1951 the trio was among the most admired small groups of the period, and its Discovery and Savoy sides carried Farlow's name well beyond New York. After Mingus left, Red Mitchell took the bass chair.

Farlow left Norvo in 1953 to spend about six months with Artie Shaw's Gramercy Five, and in 1954 he won the Down Beat New Star award, according to All About Jazz. His first records as a leader came that year: a Blue Note quartet session on April 11, with a second guitarist, Don Arnone, and a Norgran date with Barry Galbraith and Oscar Pettiford. Norgran, Norman Granz's label, then recorded him in Los Angeles in November 1954 with Ray Brown and Chico Hamilton, a session first issued as The Artistry of Tal Farlow and later reissued as Autumn in New York. By 1955 he was leading his own trio with pianist Eddie Costa and bassist Vinnie Burke, the group heard on Tal and The Swinging Guitar of Tal Farlow, and All About Jazz adds that he won the Down Beat critics poll in 1956.

In 1958 Farlow married and withdrew from the New York scene, settling in Sea Bright, New Jersey, where he went back to painting signs and played mostly local dates. Gibson built a Tal Farlow signature model with his participation in 1962. A 1969 Prestige session, The Return of Tal Farlow, was a rare studio visit, and he also joined dates produced by Don Schlitten, among them Sonny Criss's Up, Up and Away (1967) and Sam Most's Mostly Flute (1976). Xanadu issued his 1956 private recordings from the apartment of the jazz patron Ed Fuerst in 1975 and 1977, and from 1976 he recorded regularly again, mostly for Concord Jazz. A 1976 reunion with Norvo at the Concord festival, with Hank Jones and Ray Brown, became the album On Stage (1981). In 1981 Lorenzo DeStefano released a documentary, Talmage Farlow, about his life in Sea Bright, and according to DeStefano the film put him back in demand.

Through the 1980s and into the 1990s Farlow toured the United States, Europe and Japan and recorded for Concord with pianists Tommy Flanagan and James Williams and drummer Albert Heath. He took part in the Great Guitars concerts with Charlie Byrd and Herb Ellis, and in 1987 he appeared on All Strings Attached with John Abercrombie, Larry Carlton and Larry Coryell. He was diagnosed with esophageal cancer in 1997, was unable to perform in public afterward, and passed away on July 25, 1998, at Memorial Sloan-Kettering Cancer Center in New York City, at the age of 77.

Farlow came out of the line that began with Charlie Christian. The guitarist and teacher Steve Rochinski argued that, of the guitarists who emerged in the first generation after Christian, Farlow moved furthest beyond the early electric vocabulary, citing his speed, long weaving lines, rhythmic drive and advanced harmonic sense, and the critic Stuart Nicholson compared his technical command to the breaking of the four-minute mile. Where contemporaries paired rhythmic chords with single-note lines, Farlow set clusters of single notes against one another and moved among harmonically enriched tones. His very large hands gave him reach for chords few players could stretch, which earned him the nickname "the Octopus," and he used artificial harmonics and tapped the guitar body for a snare-drum or bongo effect. The mandolin-and-ukulele origin of his method left him playing melody and chords on the upper four strings and bass counterpoint with his thumb on the lower two. In later years his playing grew more lyrical and harmonically richer, with a little less of the old blazing speed. Younger guitarists named him as a formative influence, among them Larry Coryell, Al Di Meola and John McLaughlin.