Harry Haag James was born March 15, 1916, in Albany, Georgia, into a family working the Mighty Haag Circus: his father, Everett Robert James, was the circus's bandleader, and his mother, Myrtle Maybelle Stewart, was an acrobat and horseback rider. James performed in the circus himself from around age four, first as a contortionist and then on snare drum, before his father began drilling him on trumpet at eight using the Arban method. By twelve he was leading the second band of the Christy Brothers Circus. The family settled in Beaumont, Texas, in 1924, and as a teenager James won first place as trumpet soloist at the Texas Band Teachers Association contest in May 1931. His first steady professional job was at the Peabody Hotel in Memphis, where bandleader Ben Pollack heard him and hired him in 1935.

James stayed with Pollack until early 1937, then joined Benny Goodman's orchestra, where his blazing sight-reading earned him the nickname "The Hawk" and where he sat in the trumpet section alongside players who would go on to lead their own name bands. Goodman, recognizing James's talent, put up financial backing for him to leave and start his own orchestra. Harry James and His Orchestra debuted in Philadelphia in January 1939 and struggled at first. Later that spring James heard an unknown singer on a radio broadcast from the Rustic Cabin in Englewood, New Jersey, and signed him: Frank Sinatra made his first professional recordings with the James band, including "All or Nothing at All," cut August 31, 1939, and released that year to little notice (it became a million-seller only after Columbia reissued it in 1943, once Sinatra was already famous with Tommy Dorsey). Sinatra left James for Dorsey's band that November after only about six months; James, unable to match Dorsey's offer, released him from his contract without objection.

The band's fortunes turned in 1941, when James added a string section and scored his first Top Ten hit with the self-composed instrumental "Music Makers," followed that fall by "You Made Me Love You," which reached the Top Five and made James a star. Through the war years his orchestra became one of the most commercially successful in the country: "I've Heard That Song Before," cut July 31, 1942, with vocalist Helen Forrest, hit number one and sold over a million copies, and "I Had the Craziest Dream," also with Forrest, was introduced in the 1942 film Springtime in the Rockies and topped the charts for 22 weeks. James's orchestra succeeded Glenn Miller's on the Chesterfield Cigarettes radio program in 1942, and he appeared in a string of Hollywood musicals, including Private Buckaroo and Springtime in the Rockies (both 1942), Best Foot Forward (1943), and Two Girls and a Sailor (1944).

In 1943 James married actress and pin-up star Betty Grable; a 1945 U.S. Treasury report named them the highest-paid couple in the country. Their marriage lasted until 1965 and produced two daughters. James had earlier married singer Louise Tobin in 1935 (divorced 1943, two sons), and later married Joan Boyd in 1967 (divorced 1970, one son). In 1950 James dubbed the trumpet playing for Kirk Douglas in the film Young Man with a Horn, and the Columbia soundtrack album, credited to James and Doris Day, reached number one on the Billboard album chart.

As the big-band era faded commercially in the 1950s, James signed with Capitol Records in 1955 and, working increasingly with arrangements from former Count Basie saxophonist Ernie Wilkins, moved his band toward a harder-swinging, Basie-influenced sound, documented on albums including Harry James in Hi-Fi (1955) and Wild About Harry! (1957). He kept the orchestra working steadily through the 1960s and 1970s, largely as a Las Vegas and touring attraction, and continued recording for Dot, MGM, and other labels into the 1970s. Diagnosed with lymphatic cancer in 1983, James kept performing until his last engagement, June 26, 1983, in Los Angeles, and died nine days later, on July 5, 1983, in Las Vegas. Frank Sinatra delivered the eulogy at his funeral. James was inducted into the Big Band and Jazz Hall of Fame in 1983 and has a star on the Hollywood Walk of Fame, awarded February 8, 1960.

James built his technique on his father's rigorous classical drilling, but his sound came from Louis Armstrong and the blues he absorbed growing up in Texas; Armstrong himself reportedly told Lionel Hampton, on hearing James play, "That white boy, he plays like a jig." That combination gave James an instantly recognizable trumpet voice: a bravura, wide-vibrato attack, capable of both blistering high-register solos and syrupy, sentimental ballad playing, deployed with a showman's sense of when to hold a phrase and when to let a lip glissando rip. It made him one of the most commercially successful bandleaders of the swing era, and also, to many jazz critics, one of the most compromised: his post-1941 hits with strings were dismissed by some contemporaries as sentimental "schmaltz" chasing pop success rather than jazz substance, even as musicians recognized the sheer instrumental command behind it. His mid-1950s pivot toward a harder, Basie-styled book won back some critical respect and produced some of his most purely jazz-oriented recorded work.