Troy Andrews, known as Trombone Shorty, was born on January 2, 1986, and grew up in the Tremé neighborhood of New Orleans, one of seven children of James Andrews Jr. and Lois Andrews. His mother was a familiar grand marshal of second-line parades and jazz funerals; his older brother, the trumpeter and bandleader James "12" Andrews, was his first mentor; and his grandfather was the rhythm-and-blues singer and songwriter Jessie Hill. James gave him a trombone at age four because the family already had a trumpet player, and in 1990 Bo Diddley heard the four-year-old and brought him on stage at the New Orleans Jazz & Heritage Festival. By six he was leading a brass band of his own. In 1995 his brother Darnell, also a trombonist, was shot and killed, and Andrews was then looked after by his brother's manager and friend, Susan Lovejoy Scott, who guided him through his schooling and early career.

As a teenager he played in the Stooges Brass Band and studied at the New Orleans Center for Creative Arts, where his teachers included Clyde Kerr Jr. and Kent Jordan and where Jon Batiste was a schoolmate; the school's alumni also include Harry Connick Jr., Nicholas Payton and Wynton Marsalis. He graduated from Warren Easton High School in 2004. In 2003 he was one of five young musicians chosen for a PBS documentary and played on a national broadcast tribute to Louis Armstrong directed by Marsalis. His first record under his own name, Trombone Shorty's Swingin' Gate, came out in 2002 when he was sixteen, followed by 12 & Shorty with his brother in 2004 and, in 2005, two Treme Records albums: The End of the Beginning, a set of standards by the Troy Andrews Quintet, and Orleans & Claiborne, the first record by his band Orleans Avenue. In 2005 he also joined Lenny Kravitz's horn section on a world tour that shared bills with Aerosmith, and after Hurricane Katrina he was part of the New Orleans Social Club benefit recording. In 2006 he worked with producer Bob Ezrin and U2 at Abbey Road and played with U2 and Green Day at the reopening of the Louisiana Superdome.

His major-label debut, Backatown (Verve Forecast, April 20, 2010), was produced by Ben Ellman of Galactic. Andrews plays trombone and trumpet and sings on it, with Orleans Avenue behind him; it spent nine straight weeks at the top of Billboard's Contemporary Jazz Albums chart and was nominated for the Grammy for Best Contemporary Jazz Album, which went to The Stanley Clarke Band by Stanley Clarke. For True (September 13, 2011) added guests including Jeff Beck, Lenny Kravitz, Kid Rock, Warren Haynes, Ledisi, Cyril and Ivan Neville and the Rebirth Brass Band, and topped both Billboard's Jazz Albums and Contemporary Jazz Albums charts. He appeared as himself in seven episodes of the HBO series Treme between 2010 and 2013, played the White House in 2012, performed on the 2014 Grammy telecast with Macklemore and Ryan Lewis, Madonna and Queen Latifah, and was music director of the 2014 NBA All-Star halftime show in New Orleans. His third Verve album, Say That to Say This (2013), was co-produced with Raphael Saadiq.

In February 2017 he signed with Blue Note, which released Parking Lot Symphony on April 28, 2017, the opening day of that year's Jazz Fest. Produced by Chris Seefried, with Andrews credited on trombone, trumpet, vocals, keyboards, organ and several drums, it reached No. 1 on Billboard's Jazz Albums and Contemporary Jazz Albums charts. Lifted followed on April 29, 2022, recorded at his own Buckjump Studio in New Orleans, again with Seefried, with Gary Clark Jr., Lauren Daigle and the New Breed Brass Band as guests; he dedicated it to his late mother. That year he also won his first Grammy, for Album of the Year, as a featured artist on Batiste's We Are.

Since then he has turned back toward the street tradition he grew up in. The New Breed Brass Band is made up of his cousins and nephews, and a live set from the 2024 Jazz Fest credited to the band featuring Shorty was nominated for the Grammy for Best Regional Roots Music Album for 2025. Second Line Sunday, a ten-track album with the band released on Treme Records on August 29, 2025, the twentieth anniversary of Hurricane Katrina, is dedicated to his mother and earned the same nomination for 2026 (the award went to A Tribute to the King of Zydeco). On February 9, 2025, he performed "America the Beautiful" with Lauren Daigle on the field at the Caesars Superdome before Super Bowl LIX. He turned forty on January 2, 2026, and a birthday concert with guests including Leon Bridges, Joan Jett, Branford Marsalis, Irma Thomas and Mavis Staples was announced for the Saenger Theatre in New Orleans on April 25, 2026, during Jazz Fest. His picture book Trombone Shorty (2015) was named a 2016 Caldecott Honor Book, and a second, The 5 O'Clock Band, followed in 2018. He received a Heinz Award in 2016 and the Blues Music Award for horn instrumentalist in 2018. He also founded the Trombone Shorty Foundation in New Orleans, whose programs, according to the foundation, include the Trombone Shorty Academy, a music business institute and a cultural exchange with Cuba.

Andrews plays trombone and trumpet at a big, brash brass-band volume and also sings, and he is at home on organ, drums, tuba and keyboards. He calls his blend "supafunkrock," a New Orleans gumbo of second-line rhythm, funk, rock, hip-hop, soul and jazz, and he has said that musicians should build on earlier music rather than copy it. Where that puts him relative to jazz depends on the yardstick. His records have been issued by Verve Forecast and Blue Note, have topped Billboard's jazz charts, and drew a Contemporary Jazz Grammy nomination, and his roots are in New Orleans brass-band and second-line music and in his brother James's jazz band. His own stage show and his touring partners (Lenny Kravitz, Foo Fighters, Red Hot Chili Peppers) sit closer to funk and rock, and his recent Grammy nominations have been in the regional roots category. Critics have praised his live energy more than his studio polish: Nate Chinen of the New York Times found Backatown less thrilling than the shows, and reviewers of Parking Lot Symphony split on whether the formula had worn thin. He names his brother James, Cyril Neville, Wynton Marsalis, Kermit Ruffins, Walter "Wolfman" Washington, Allen Toussaint and Lenny Kravitz as mentors. Through the Trombone Shorty Foundation, the Horns for Schools instrument drive begun with Mayor Mitch Landrieu, and his work with the New Breed Brass Band, he has in turn become a teacher of younger New Orleans players, and he describes himself first of all as a New Orleans musician.