[2] Williams wrote and arranged for Duke Ellington and Benny Goodman, and she was friend, mentor, and teacher to Thelonious Monk, Charlie Parker, Miles Davis, Tadd Dameron, Bud Powell, and Dizzy Gillespie.

The second of eleven children, Williams was born in Atlanta, Georgia, and grew up in the East Liberty neighborhood of Pittsburgh, Pennsylvania.

The group, Andy Kirk's Twelve Clouds of Joy,[11] moved to Tulsa, Oklahoma, where Williams, when she wasn't working as a musician, was employed transporting bodies for an undertaker.

When the Clouds of Joy accepted a longstanding engagement in Kansas City, Missouri, Williams joined her husband and began sitting in with the band, as well as serving as its arranger and composer.

She provided Kirk with such songs as "Froggy Bottom", "Walkin' and Swingin'", "Little Joe from Chicago", "Roll 'Em", and "Mary's Idea".

Soon after the recording session she became Kirk's permanent second pianist, playing solo gigs and working as a freelance arranger for Earl Hines, Benny Goodman, and Tommy Dorsey.

In 1937, she produced In the Groove (Brunswick), a collaboration with Dick Wilson, and Benny Goodman asked her to write a blues song for his band.

[15] She was joined there by bandmate Harold "Shorty" Baker, with whom she formed a six-piece ensemble that included Art Blakey on drums.

She traveled with Ellington and arranged several tunes for him, including "Trumpet No End" (1946), her version of "Blue Skies" by Irving Berlin.

[17] "During this period Monk and the kids would come to my apartment every morning around four or pick me up at the Café after I'd finished my last show, and we'd play and swap ideas until noon or later", Williams recalled in Melody Maker.

[18] She recorded the suite with Jack Parker and Al Lucas and performed it December 31, 1945, at The Town Hall in New York City with an orchestra and tenor saxophonist Ben Webster.

In addition to spending several hours at Mass, her energies were then devoted mainly to the Bel Canto Foundation, an effort she initiated using her savings as well as help from friends to turn her apartment in Hamilton Heights into a halfway house for the poor as well as musicians who were grappling with addiction; she also made money over a longer period of time for the halfway house by way of a thrift store in Harlem.

In addition to club work, she played at colleges, formed her own record label and publishing companies, founded the Pittsburgh Jazz Festival (with the bishop's help), and made television appearances.

[22]Following her hiatus, Willams' first piece of music was a Mass she wrote and performed named Black Christ of the Andes, based around a hymn in honor of the Peruvian saint Martin de Porres, and two other short works, Anima Christi and Praise the Lord.

As a 1964 Time article explained, "Mary Lou thinks of herself as a 'soul' player — a way of saying that she never strays far from melody and the blues, but deals sparingly in gospel harmony and rhythm.

With a light teaching schedule, she also made many concert and festival appearances, conducted clinics with youth, and in 1978 performed at the White House for President Jimmy Carter and his guests.

[15] Williams' final recording, Solo Recital (Montreux Jazz Festival, 1978), three years before her death, had a medley encompassing spirituals, ragtime, blues and swing.

Other highlights include Williams's reworkings of "Tea for Two", "Honeysuckle Rose", and her two compositions "Little Joe from Chicago", and "What's Your Story Morning Glory".

Other tracks include "Medley: The Lord Is Heavy", "Old Fashion Blues", "Over the Rainbow", "Offertory Meditation", "Concerto Alone at Montreux", and "The Man I Love".

[35] Her final work for wind symphony, History..., reconstructed and recomposed by Duke faculty member Anthony Kelley, was premiered in 2024.