Sharel Cassity grew up moving from place to place before her family settled in Yukon, Oklahoma, where she finished high school in 2000. Her first competitive success was at the keyboard, not the horn: she placed third in the Disney International Piano Concerto Competition at ten. By eighteen she was good enough on classical saxophone to be offered a full scholarship to North Texas State University. She turned toward jazz instead, moved to New York City in 2000, and took her BFA at the New School for Jazz and Contemporary Music in 2005, having earlier attended the University of Central Oklahoma. Along the way she was picked for three of the competitive young-musician programs that function as a farm system for the American jazz scene: the IAJE Sisters in Jazz collective, Betty Carter's Jazz Ahead at the Kennedy Center, and the Ravinia Festival's Steans Institute residency. In 2007 she completed a master's degree at the Juilliard School on full scholarship, and the same year took the ASCAP Young Jazz Composers Award.

The New York decade that followed was built on big bands. She joined the DIVA Jazz Orchestra, Sherrie Maricle's all-women big band, as lead alto in 2007 and held that chair for roughly seven years, a tenure her own materials date to 2014 and Wikipedia to 2013. In 2008 she became a member of the Dizzy Gillespie All-Star Big Band, the repertory ensemble run by bassist John Lee, and of the Roy Hargrove Big Band. From 2012 to 2020 she worked in NEA Jazz Master Jimmy Heath's big band and in the Queens Jazz Orchestra, and she spent 2011 and 2012 in Nicholas Payton's big band. She played Wynton Marsalis's Broadway production After Midnight, and the Jazz at Lincoln Center orbit took her to Doha in 2015 and Shanghai in 2016; that same year she played Rose Hall and the New York Botanical Garden with the Lincoln Center Jazz Orchestra. In 2017 she was at the Kennedy Center with Herbie Hancock for Jimmy Heath's ninetieth birthday. Outside the jazz world she toured with Natalie Merchant in 2014 and 2015, appearing on the Today Show and on Merchant's Paradise Is There project, and has worked with Jennifer Hudson, Aretha Franklin, Vanessa Williams, Trisha Yearwood and Ruben Blades.

Her recording career as a leader began in 2008 with Just for You, cut in Brooklyn on March 19 of that year for the small DW Records imprint, with trombonist Michael Dease producing, Adam Birnbaum on piano and Vince Ector on drums. Ingrid Jensen wrote the liner notes. Relentless followed on Jazz Legacy Productions in 2009, recorded across four days in September 2008 in Union City and South Orange, New Jersey, with Jeremy Pelt on trumpet, Dease on trombone, Orrin Evans on piano, Dwayne Burno on bass and E.J. Strickland on drums. John Lee produced and mixed it, Paul Wickliffe mastered it, and six of its eight titles are Cassity originals. It drew four stars in DownBeat and reached number 21 on the JazzWeek national jazz chart. Five years later the Japanese label Venus put out Manhattan Romance, a standards program taped in New York on February 26, 2014 by a quartet of Cyrus Chestnut, Rufus Reid and Lewis Nash, produced by Todd Barkan and Tetsuo Hara.

In 2016 she left New York for the Chicago area, founding her own label, Relsha Music, the same year. Its first release, Evolve (April 2018), is credited to Sharel Cassity & Elektra and is the outlier in her catalog: an electric, genre-crossing record with Miki Hayama on keyboards and synthesizer, Linda Oh on bass, Mark Whitfield on guitar, Riza Printup on harp, Ingrid Jensen and Marcus Printup on trumpet and Christie Dashiell singing, mixing seven Cassity originals with readings of Alicia Keys's "New Day" and Bjork's "All Is Full of Love." In summer 2019, after a run of false negatives, she was diagnosed with Lyme disease, and spent months with severe neurological symptoms, body weakness and mental fog. She kept working through it, switching to softer reeds and playing international dates with intravenous ports in her arms. By January 2020 she had recovered enough to run new charts with a band at Smalls in New York, and the result was Fearless (Relsha Music, August 13, 2020), a quartet date with Richard D. Johnson, Alexander Claffy and Mark Whitfield Jr. Its "Ballad for Roy" is for Roy Hargrove, who had died in 2018; Cassity has said she took her horn out the day he passed away and the melody came from that. Howard Reich put the album on the Chicago Tribune's best jazz recordings of 2020.

Chicago also produced two collaborative records. Altoizm (2021) is a three-alto meeting with Rajiv Halim and Greg Ward, taped January 7, 2021 at the Jazz Place in Carpentersville, Illinois, with Richard Johnson at the piano and doubling as engineer. Alliance (Shifting Paradigm, March 2024) is co-led with drummer Colleen Clark, a quartet reading of Mulgrew Miller, Mary Lou Williams, Jimmy Heath, Herbie Hancock and Harold Mabern alongside band originals, with liner notes by Michael Dease. Her most recent leader album, Gratitude, came out on Sunnyside on March 28, 2025 from a single session recorded May 8, 2023 at the Bunker Studio in Brooklyn: Cyrus Chestnut on piano, Christian McBride on bass, Lewis Nash on drums, and Terell Stafford and Dease added on two tracks. Cassity co-produced it with John Lee. DownBeat had named her Rising Star Alto Saxophone in its 2023 critics poll and ran her on the cover; she is an Oklahoma Jazz Hall of Fame inductee, and she has toured 24 countries.

Teaching has run in parallel throughout. She has taught in Qatar, Japan, Costa Rica, Mexico and China, and in the Chicago years held faculty positions at DePaul University, Columbia College Chicago and Elgin Community College, where she taught saxophone, flute and piano. In 2018 she started Jazz Up!, a nonprofit outreach program for high school jazz students. In 2025 she moved again, to Charlottesville, Virginia, as Associate Professor of Music and Director of Jazz Performance at the University of Virginia, succeeding trumpeter John D'Earth, who had retired that January. She remains in the Dizzy Gillespie All-Star Big Band and its Latin offshoot, and endorses Yamaha saxophones and flutes and Vandoren reeds.

Cassity is an alto player first, with a hard-bop attack that reviewers reliably describe as fiery and soulful, and her writing sits in the same territory: heads with real melodic shape, built for a horn-and-rhythm band rather than for texture. Her mentors are the ones she names, and they are all from the bebop line she came up inside: Roy Hargrove, Jimmy Heath and James Moody, all of whom she also worked for. What distinguishes her from a straight-ahead alto specialist is the size of the doubling arsenal. She plays soprano and tenor as well as alto, and flute, alto flute, piccolo, clarinet and bass clarinet, and she is hired for that range: the flute and alto flute carry parts of Relentless and Alliance, and on Yotam Silberstein's Brasil she was brought in purely as an alto flute and clarinet voice, with no saxophone credit at all. Her one deliberate departure from the acoustic quartet format, the Elektra band on Evolve, adds harp, synthesizer and a vocalist and reworks Alicia Keys and Bjork, which is the same instinct pointed at different repertoire. DownBeat listed her in its Rising Star Alto Saxophone category for a dozen consecutive years before she won it in 2023.