Hardin was born as Lillian Hardin in Memphis, Tennessee. In her youth she learned hymns, spirituals, and light Classics on the piano. She was drawn to popular music and later blues, but could only listen or play these styles occasionally covertly, as her family considered them "sinfull". While she sometimes claimed to be a valadictorian graduate of Fisk University, records show that Hardin actually attended for less than a year without receiving a degree.
Lil Hardin moved to Chicago in 1917. Her talent for playing tunes well at first sight got her a job demonstrating sheet music at a the Jones Music Store. Her third week on the job Jelly Roll Morton walked in the store and played the piano, making jazz variations on the tunes Lil had been playing. This had a profound effect on Lil, and she made her best efforts to play in a jazz style. Her performances at the music store began to draw crowds, and she was offered a job playing with Sugar Johnny Smith's Creole Band, a group of musicians from New Orleans. She then worked with the bands of Freddie Keppard, led her own band for a while, then in 1921 was hired by "King" Joe Oliver to play in his famous band.
In 1922 Oliver sent to New Orleans for his young protoge to join the band on second cornet. The young man was Louis Armstrong. Lil was initially unimpressed with Louis, who arrived in Chicago wearing clothes considered long out of style in the northern city, but with time he grew on her and a romance developed (to the surprise of other band members, some of whom had been trying to woo pretty Lil for some time with no success). Lil married Louis Armstrong on February 4, 1924.
Lil taught Louis how to dress and act in sophisticated modern style. While Louis was content playing in the band of his mentor, Lil encouraged him to leave Oliver and become a star in his own right. Armstrong resigned from Oliver's band (Lil stayed to assure income during the transitional period). Unfortunately Louis Armstrong was unable to find steady work in Chicago under his own name, and so in September of 1924 accepted a job offer from Fletcher Henderson in New York City. Lil stayed in Chicago, first with Oliver, then leading a band of her own. When Lil's band got a job at the well known Dreamland danceclub the following year, Louis returned to Chicago to join her band.
Louis soon became famous in Chicago, and Richard M. Jones convinced Okeh Records to hire Louis Armstrong to do a series of recordings, thus the famous Louis Armstrong & His Hot 5 series of recordings began in November of 1925, featuring Lil on piano; the rest of the band were musicians Armstrong had worked with back in New Orleans.
Lil also recorded on the side with other jazz groups in Chicago, often with Johnny Dodds.
In the late 1920s Lil and Louis grew apart. Armstrong formed a new Hot 5, with Earl Hines on piano. Lil reformed her own band with Freddie Keppard on cornet (who Lil considered the second best jazz trumpeter after her husband). Louis and Lil separated in 1931, though they remained friends.
In the 1930s Lil Hardin Armstrong led an "All Girl Orchestra", then a mixed gender Big Band which broadcast nationally over the NBC radio network. The same decade she recorded a series of sides for Decca Records as a Swing vocalist, as well as appearing as a piano accompaniest for many other singers. She also recorded with Red Allen.
In the late 1940s and early 1950s she worked mostly as a soloist singing and playing piano. He projects on the side included appearing in Broadway shows and staging a fashion show. Lil again started leading a jazz band in the mid '50s, and toured Europe before returning to Chicago.
Lil Hardin Armstrong died while taking part in a memorial concert for Louis Armstrong, who had died the previous month.
Lil Hardin Armstrong's compositions include " Struttin' With Some Barbecue", "Don't Jive Me", "Two Deuces", "Knee Drops", "Doin' the Suzie-Q", ""Just For a Thrill", "Clip Joint", and "Bad Boy"; a cover record of the last number by Ringo Starr was a hit in 1978.