Charles Henry Christian was born on July 29, 1916, in Bonham, Texas, and grew up in Oklahoma City, where the family moved when he was a small child. His parents were musicians, and his father, Clarence Henry Christian, who had been blinded by a fever, taught music to his sons Edward (born 1906), Clarence (born 1911), and Charlie. The family earned money as street buskers, with the boys leading their father into the better neighborhoods to play for cash or goods; Charlie first entertained by dancing, then learned guitar, and he inherited his father's instruments when his father died, when he was 12. At Frederick A. Douglass High School he wanted to play tenor saxophone in the band, but the music teacher Zelia N. Breaux put him on trumpet instead. He quit the instrument, worried that it would damage his lip, and turned to baseball, at which he excelled.

Around 1931 the trumpeter James Simpson had the guitarist Ralph "Bigfoot" Hamilton quietly teach the teenager to solo on "Rose Room," "Tea for Two," and "Sweet Georgia Brown." Hamilton then brought him to an after-hours jam session in Oklahoma City's Deep Deuce district, where his older brother Edward, a pianist and bandleader, was working, and the boy's command of the tunes surprised his brother. Christian soon played locally and on the road across the Midwest, as far afield as North Dakota and Minnesota, and by 1936 he was using an electric guitar and was a regional attraction. According to the record producer John Hammond, he jammed with touring stars who came through Oklahoma City, among them pianist Teddy Wilson, pianist Art Tatum, and Mary Lou Williams, then the pianist with Andy Kirk and His Clouds of Joy.

In 1939 Christian auditioned for Hammond, who recommended him to the bandleader Benny Goodman. Accounts of the first meeting differ, but the story of his first night in the band is consistent: at the Victor Hugo restaurant in Los Angeles, Goodman called "Rose Room," assuming the newcomer would not know it, and Christian took twenty choruses and was hired. His pay went from about $2.50 a night to $150 a week. He joined the newly formed Goodman Sextet in September 1939, alongside vibraphonist Lionel Hampton, pianist Fletcher Henderson, bassist Artie Bernstein, and drummer Nick Fatool. The sextet's first Columbia session was held in New York on October 2, 1939, and produced "Flying Home" and "Rose Room"; on November 22, 1939, it recorded "Seven Come Eleven," a tune credited jointly to Goodman and Christian. By February 1940 he dominated the guitar polls and had been elected to the Metronome All-Stars, and on February 7, 1940, he took part in the second Metronome All-Stars recording session at Columbia Studios alongside drummer Gene Krupa and other poll winners. The sextet also recorded that month with Count Basie at the piano. Goodman laid off most of his orchestra in spring 1940 but kept Christian, and that fall the sextet featured trumpeter Cootie Williams and tenor saxophonist Georgie Auld, with drummer Dave Tough joining later; the group dominated the 1941 polls. Christian also played with the full orchestra, notably on "Solo Flight," recorded on March 4, 1941, with a composer credit shared among Christian, arranger Jimmy Mundy, and Goodman. The record was released in early 1944 and reached number sixteen on the pop charts and number one on the Harlem Hit Parade. Though credited on few of them, he composed many of the sextet's original tunes; "Air Mail Special" is credited to Goodman, Mundy, and Christian.

The sextet was Christian's public life; Harlem after dark was his other one. Joining the late-night sessions at Minton's Playhouse, at 210 West 118th Street, he played among the musicians who were building bebop, including Dizzy Gillespie and Thelonious Monk, a regular in the club's house band. In 1941 Jerry Newman, a Columbia University student with a portable disc recorder, captured Christian at Minton's with trumpeter Joe Guy, pianist Kenny Kersey, and drummer Kenny Clarke, and at Clark Monroe's Uptown House with trumpeter Oran "Hot Lips" Page; tenor saxophonist Don Byas also appears on some of the material. Those discs have been issued under many titles, including After Hours and The Immortal Charlie Christian. Some people at Minton's credited him with the name "bebop," saying it came from phrases he hummed, and Clarke later said that "Epistrophy" and "Rhythm-a-Ning," credited to Monk, were actually Christian's, recalling that Christian first showed him the chords to "Epistrophy" on a ukulele.

Christian contracted tuberculosis in the late 1930s and was briefly hospitalized in early 1940, when Goodman's own back trouble left the band idle. He went home to Oklahoma City in late July 1940 and returned to New York in September, then kept up a punishing schedule in early 1941, working with Goodman and heading to Harlem for jam sessions afterward. In June 1941 he was admitted to Seaview Hospital, a tuberculosis sanatorium on Staten Island. He seemed to be improving, and DownBeat reported in February 1942 that he and Cootie Williams were planning a band, but after a visit from a musician friend later that month his condition worsened. He passed away of tuberculosis on March 2, 1942, at the age of 25, and was buried in an unmarked grave in Bonham. A Texas State Historical Commission marker and headstone were placed in Gates Hill Cemetery in 1994; in March 2013 Fannin County recognized that the marker stood in the wrong place and that, as his brother Clarence had said, he lies under a concrete slab.

He remained at the top of the guitar polls for up to two years after his death and was inducted into the DownBeat Jazz Hall of Fame in 1966, the Oklahoma Jazz Hall of Fame in its first class of 1989, and the Rock and Roll Hall of Fame in the Early Influence category in 1990. In 2006 Oklahoma City renamed a street in its Bricktown district Charlie Christian Avenue. He never recorded as a leader; everything he left was made as a sideman, in broadcasts and amateur recordings, or in the jam sessions that Newman and others happened to catch.

Christian is widely regarded as one of the most influential pioneers of jazz guitar. His solos are often described as horn-like: he said he wanted his guitar to sound like a tenor saxophone, and he drew more from horn players such as Lester Young and Herschel Evans than from guitarists like Eddie Lang or Lonnie Johnson. The French guitarist Django Reinhardt had little influence on him, though he knew some of Reinhardt's records. Electric guitar soloists had been recorded before 1939, among them Leonard Ware, Eddie Durham, and Floyd Smith, but Christian's single-string technique and early use of amplification moved the guitar out of the rhythm section and into the front line, and he is often credited with pioneering the lead-guitar role. The Minton's and Monroe's recordings show him taking many choruses on one tune and playing long stretches of melodic ideas, using tension and release in the manner of Lester Young and Count Basie. Ballads such as "Stardust," "Memories of You," and "On the Alamo" with the sextet, and "Profoundly Blue" with the Edmond Hall Celeste Quartet (1941), hint at what would later be called cool jazz. His influence on Dizzy Gillespie, Charlie Parker, Thelonious Monk, and Don Byas can be heard in their early bop records, and Miles Davis also cited him as an early influence. Among guitarists, Barney Kessel, Wes Montgomery, Tal Farlow, and Jim Hall each name him as a starting point, and his reach extended past jazz to T-Bone Walker, B.B. King, Chuck Berry, Carlos Santana, and Jimi Hendrix. John Hammond and the critic George T. Simon both called him the best improvising talent of the swing era. His guitars were Gibson models, first an ES-150 with its EH-150 amplifier and later custom ES-250 instruments; the bar pickup on the ES-150 and ES-250 became known as the "Charlie Christian pickup."