Arthur Tatum Jr. was born October 13, 1909, in Toledo, Ohio, to Mildred Hoskins, a domestic worker from Virginia, and Arthur Tatum Sr., a mechanic from North Carolina. He had impaired vision from infancy, likely caused by cataracts, and by age eleven, after several operations, could see only close objects and distinguish colors; an assault in his early twenties left him blind in one eye and severely limited in the other. He learned piano largely by ear, showing perfect pitch and an exceptional memory from childhood. He attended Toledo's Jefferson School, briefly enrolled at the School for the Blind in Columbus, Ohio in late 1924, and then transferred to the Toledo School of Music, where the visually impaired classical pianist Overton G. Rainey gave him formal lessons but discouraged jazz; Tatum taught himself the jazz idiom from radio, records, and piano rolls, absorbing Fats Waller, James P. Johnson, Earl Hines, and the semi-classical pianist Lee Sims along the way.

Tatum began performing professionally around Toledo in the mid-1920s and, after winning an amateur contest in 1927, hosted a daily program on local radio station WSPD that was carried nationally by the Blue Network in 1928-29. Touring musicians including Duke Ellington and Fletcher Henderson heard him in Toledo and were impressed, but Tatum felt unready for New York. In 1932 the singer Adelaide Hall, passing through Toledo, recruited him for her band; on August 5, 1932, he made his first studio recordings backing Hall, and on his arrival in New York he took part in a celebrated cutting contest at a Harlem venue against stride masters James P. Johnson, Fats Waller, and Willie "The Lion" Smith, playing arrangements of "Tea for Two" and "Tiger Rag" that reportedly left Johnson startled by what could be done with a familiar tune. His first solo studio recordings followed in March 1933 for Brunswick, including "Tiger Rag," "St. Louis Blues," "Sophisticated Lady," and "Tea for Two." Through the rest of the 1930s he worked residencies in New York (including his first solo job at the Onyx Club on 52nd Street), Cleveland, a year-long stand at Chicago's Three Deuces beginning in 1935, and Los Angeles, recording for Decca and Brunswick along the way. In 1938 he toured England for three months, appearing twice on BBC television.

Tatum formed a trio with guitarist Tiny Grimes and bassist Slam Stewart in 1943 that became one of the most commercially successful acts on 52nd Street, though he disbanded it in 1944 and did not lead another trio for eight years, preferring solo work; by early 1945 the Downbeat Club was reportedly paying him an unusually high $1,150 a week for solo sets. He won Esquire magazine's 1944 critics' poll for pianists and began playing formal concert halls that year as wartime conditions changed the entertainment business. His sextet side "Wee Baby Blues," with vocalist Big Joe Turner, sold roughly 500,000 copies in 1941, and a set of informal 1940-41 recordings later released as God Is in the House earned him a posthumous Grammy Award in 1974 for the 1973 recording year. He signed to Capitol Records at the end of the decade, recording 26 sides for the label beginning with a 1949 Los Angeles concert issued as Gene Norman Presents an Art Tatum Concert, and continuing with studio sessions issued as Art Tatum (1950) and Art Tatum Encores (1951). He reunited with Slam Stewart, now alongside guitarist Everett Barksdale, in a trio that recorded for Capitol in 1952 and toured with pianists Erroll Garner, Pete Johnson, and Meade Lux Lewis on a 1952 "Piano Parade" package tour. His popularity had cooled somewhat by the late 1940s as bebop, a style he never adopted, reshaped jazz's mainstream, though musicians continued to revere him.

Producer Norman Granz brought Tatum into the studio in late 1953 with an unprecedented brief: play whatever he wished. Over several sessions Tatum recorded 124 solo tracks, all but three of them released across what became an eleven-LP Clef Records series, The Genius of Art Tatum, later reissued complete as The Complete Pablo Solo Masterpieces; the series entered the Grammy Hall of Fame in 1978. Granz followed with seven further sessions between 1954 and 1956 pairing Tatum with other major jazz figures, yielding 59 tracks eventually reissued as eight Tatum Group Masterpieces volumes: trios with altoist Benny Carter and drummer Louie Bellson (The Tatum-Carter-Bellson Trio, Clef, 1955) and with vibraphonist Lionel Hampton and drummer Buddy Rich (The Lionel Hampton-Art Tatum-Buddy Rich Trio, Clef, 1956), a further Hampton-led session with Harry Edison, Rich, Red Callender, and Barney Kessel, a quartet with trumpeter Roy Eldridge (Clef, 1955), a reunion trio with Stewart and Barksdale, and quartets fronted by clarinetist Buddy DeFranco and tenor saxophonist Ben Webster (both Verve, 1958, recorded 1956). Critical response to the group sessions was mixed at the time, some writers finding the material unadventurous, but Tatum won DownBeat's critics' poll for pianists three years running starting in 1954. He toured with Stan Kenton's orchestra on its 1954 "Festival of Modern American Jazz," and appeared on television that April on The Spike Jones Show, one of the few surviving filmed records of his playing. His only film appearance had come earlier, in 1947's The Fabulous Dorseys.

Tatum stopped drinking in 1954 as his health declined, divorced his first wife Ruby Arnold in early 1955 after twenty years of marriage, and married Geraldine Williamson later that year. In August 1956 he played for the largest audience of his career, roughly 19,000 people at the Hollywood Bowl in a Granz-produced event, and the following month recorded his final studio session with Ben Webster. Too ill to continue touring, he returned home to Los Angeles, where musician friends gathered at his bedside on November 4, 1956; he died of uremia the next day, November 5, 1956, at age 47, at Queen of Angels Medical Center. He was inducted into the DownBeat Jazz Hall of Fame in 1964 and received a Grammy Lifetime Achievement Award in 1989, and Toledo has since honored him with a resource center at its Kent Branch Library (1989), a historical marker at his childhood home (2003), and a public sculpture (2009).

Tatum's technique was harmonically some three decades ahead of the jazz mainstream of his time: he layered dense substitute chords, extended harmony into elevenths and thirteenths, occasionally played in two keys at once, and expanded stride piano's left-hand vocabulary with tenths and wider intervals, all delivered with a clean, unhurried touch even at extreme tempo. Rather than build new melodic lines over a tune's changes, he tended to state or imply the original melody while layering fragmentary countermelodies and rhythmic displacement around it, and he could shift the number of notes per beat without losing the underlying pulse. Musicians rather than the general public first recognized what he had done: Charlie Parker reportedly took a dishwashing job at a club where Tatum played to study him at close range, Dizzy Gillespie cited his speed and harmonic daring as a spur to bebop's own ambitions, Coleman Hawkins dated his own stylistic development to hearing Tatum in Toledo in the 1920s, and pianists from Bud Powell and Oscar Peterson to Herbie Hancock and Chick Corea learned directly from his recordings; Mary Lou Williams credited him with teaching her how to control her touch without relying on the pedal. Some critics, including Gary Giddins, have argued his dense, non-linear style keeps casual listeners at arm's length, which Giddins suggests helps explain why his broader popular standing has never quite matched his standing among musicians.