Ferdinand Joseph LaMothe was born in the Creole community of the Faubourg Marigny in New Orleans, the son of Edward Joseph LaMothe, a bricklayer and occasional trombonist, and Louise Monette, a domestic worker. His parents were never legally married, no birth certificate was ever issued, and the date of his birth is unsettled: a baptismal register at St. Joseph's Church records October 20, 1890, with baptism on April 25, 1891, while Morton told Alan Lomax he was born in 1885 and gave 1884 on his 1918 draft registration card. After his mother married William Mouton in 1894 he took the anglicized surname Morton. At about fourteen he began playing piano in a brothel in the Storyville district, where he took the nickname Jelly Roll, and his churchgoing great-grandmother, who had believed he worked as a night watchman, disowned him when she found out.

Around 1904 he began touring the South with minstrel shows such as Will Benbow's Chocolate Drops, gambling and composing; "Jelly Roll Blues," "New Orleans Blues," "Frog-I-More Rag," "Animule Dance," and "King Porter Stomp" all date from this period. The stride pianists James P. Johnson and Willie "The Lion" Smith heard him play in Chicago in 1910 and in New York in 1911. He toured vaudeville with his girlfriend Rosa Brown in 1912 to 1914, lived in Chicago for about three years, and by 1914 was writing his compositions down; "Jelly Roll Blues," published in 1915, is counted among the first published jazz compositions. In 1917 he went to California with the bandleader William Manuel Johnson and Johnson's sister Anita Gonzalez, played the Hotel Patricia in Vancouver, and spent years as an itinerant pianist, vaudeville performer and gambler. He returned to Chicago in 1923 to claim authorship of "The Wolverines," which had become popular as "Wolverine Blues."

His recording career began that year. "King Porter Stomp" was first recorded as a piano solo in 1923, and on July 17 and 18, 1923 he joined the New Orleans Rhythm Kings for Gennett sessions, an early example of a racially mixed recording date. In 1924 he recorded a duet version of "King Porter Stomp" with the cornetist King Oliver. In 1926 he signed with the Victor Talking Machine Company, which let him bring a rehearsed band into its Chicago studio to play his arrangements. Jelly Roll Morton and His Red Hot Peppers recorded "Black Bottom Stomp" on September 15, 1926, "Dead Man Blues" on September 21, and "Original Jelly-Roll Blues" and "Doctor Jazz" on December 16, with a pool of New Orleans players including Kid Ory, Omer Simeon, George Mitchell, Johnny St. Cyr, Barney Bigard, Johnny Dodds and Baby Dodds. He married the showgirl Mabel Bertrand in November 1928 and moved to New York, where he kept recording for Victor with horn players such as Bubber Miley, Henry "Red" Allen, Albert Nicholas and Zutty Singleton, though he had trouble finding musicians who wanted to play his style and the New York sessions produced no hit.

Victor did not renew his contract for 1931, a casualty in part of the Depression, and Morton struggled financially, with a brief radio show in 1934 and a stint in a burlesque band. In 1935 his three-decade-old "King Porter Stomp," arranged by Fletcher Henderson, became Benny Goodman's first hit and a swing-era standard, and Morton earned no royalties from it. That year he moved to Washington, D.C., to manage and play piano at a U Street bar variously called the Music Box and the Jungle Inn, where the folklorist Alan Lomax heard him. Lomax invited him to the Library of Congress, and the sessions in the Coolidge Auditorium began on May 23, 1938 and grew into more than eight hours of talk and piano about Storyville, early jazz and his own career, later the basis of Lomax's 1950 book Mister Jelly Roll. Some of the bawdier songs stayed unreleased until 2005. In 1938 he was stabbed by an associate of the club's owner and was refused treatment at a nearby whites-only hospital, and he never fully recovered. After a spell in a New York hospital for asthma he recorded again in 1939 and 1940, including a Victor date on September 14, 1939 with Sidney Bechet on soprano saxophone, and then travelled to Los Angeles to restart his career. He passed away at Los Angeles County General Hospital on July 10, 1941, after an eleven-day stay. Kid Ory, Mutt Carey, Fred Washington and Ed Garland were pallbearers at a funeral that few prominent musicians attended; Duke Ellington and Jimmie Lunceford were both in Los Angeles at the time but absent.

Recognition came mostly after his death. The 2005 Rounder set of the Lomax recordings won two Grammy Awards at the 2006 ceremony, for Best Historical Album and Best Album Notes, and Morton was in the 2005 class of Grammy Lifetime Achievement Award recipients. His 1928 Victor single "Kansas City Stomps" and the album The Saga of Mr. Jelly Lord are in the Grammy Hall of Fame, "Black Bottom Stomp" and the 1938 Lomax interviews are in the Library of Congress National Recording Registry, and he is in the Rock and Roll Hall of Fame and the Louisiana Music Hall of Fame (2008) and is a charter member of the Gennett Records Walk of Fame. The musical Jelly's Last Jam, built on his music and life, reached Broadway in 1992 and earned him a posthumous Tony Award nomination for Best Original Score.

Morton is often called jazz's first arranger, the man who showed that a music rooted in improvisation could keep its character when written down. His piano style grew out of early ragtime and the "shout" tradition and sat close to barrelhouse; he often carried the melody with his right thumb while the fingers laid a harmony above it, walked the left hand in sixths rather than tenths or octaves, and swung with both hands. His band writing balanced composed passages against solo space, with breaks, stop-time choruses, collective improvisation and a stomping final strain, and he insisted that real jazz needed what he called the Spanish tinge, the habanera and tango rhythmic flavor audible in "Original Jelly-Roll Blues" and "Black Bottom Stomp." He also claimed to have invented jazz in 1902, a boast critics have debated: Scott Yanow argued it hurt his posthumous reputation, while Gunther Schuller held that his achievements made it credible. His music passed into the swing era through Fletcher Henderson's arrangement of "King Porter Stomp" for Benny Goodman, and later arrangers returned to it, among them Gil Evans on a 1975 version, while Henry Threadgill's trio Air devoted the 1979 album Air Lore to Morton and Scott Joplin. The pianist Dick Hyman and the composer Reginald Robinson are named as carrying his influence forward, and the melody of his 1926 "Sweet Peter" appears to be the source of the 1931 hit "All of Me."