Deborah Weisz was born June 20, 1962, in Chicago, Illinois, and grew up in Phoenix, Arizona, where she took up the trombone at age ten. At Alhambra High School her band director, Pat Lebs, had her sing melodies before playing them, a lesson in phrasing she has credited ever since. After earning an A.A. in Music Performance from Mesa Community College in 1982, she moved to Las Vegas to finish a B.A. in Music Performance at the University of Nevada, Las Vegas in 1984.

Weisz spent roughly eleven years based in Las Vegas working as a freelance musician in production shows and behind touring headliners, a stretch she has called her real "trombone school": the city's studio and show bands were full of veterans who had toured with Stan Kenton, Woody Herman, Buddy Rich, Count Basie and Duke Ellington, and she absorbed their road stories alongside their playing. The most significant of those mentors was Carl Fontana, with whom she studied and performed for years. From 1987 to 1994 she toured internationally as a member of Frank Sinatra's band.

She relocated to New York City in 1993 and built a career that ran in parallel across Broadway pits, studio and film-scoring dates, and jazz bandstands. Her working associations included small-group dates with Freddie Hubbard, Don Braden, Fred Hersch and Sonny Fortune, and chairs in the big bands of Jimmy Heath, Sherrie Maricle's DIVA Jazz Orchestra, and composer Jamie Begian's ensemble. She also became a longtime collaborator of trombonist Roswell Rudd, touring with his Trombone Shout Band to the Festival au Désert near Timbuktu, Mali, in 2004, and appearing among the dozen trombonists Rudd assembled for his own 2009 Sunnyside album Trombone Tribe, alongside players including Ray Anderson, Wycliffe Gordon and Steve Swell.

Weisz earned a Master of Arts in Music Composition from New York University, where she studied with pianist and composer Jim McNeely (on a 1989 NEA study grant awarded before her formal enrollment) and with Bob Brookmeyer. Her own writing won the Julius Hemphill Jazz Composition Contest in 2000, was a finalist for the BMI Foundation/Charlie Parker Composition Award in 2001, and received a New England Foundation for the Arts Meet the Composer commission in 2004. She released her debut as a leader, Breaking Up, Breaking Out, on her own Va Wah label in 1997, and followed it in 2005 with two more Va Wah dates: Trio, with bassist Nicki Parrott and guitarist Sheryl Bailey, and Grace (For Will), a quintet session with special guest Olivier Ker Ourio on chromatic harmonica, for which McNeely both contributed a composition and wrote the liner notes.

In the 2000s and 2010s her sideman work included one of the two trombone chairs, alongside Jonathan Voltzok, on Noir (2007), the sole album by Anat Cohen's The Anzic Orchestra; a credit on Anthony Braxton's mass-tuba piece Composition No. 19 (For 100 Tubas) (2011); and three albums with saxophonist Jon Schapiro's big band Schapiro 17, running from New Shoes: Kind of Blue at 60 (2020) through Best Laid Plans (2026). She has continued to perform and record with DIVA Jazz Orchestra, including its 2014 MCG Jazz release A Swingin' Life.

Weisz has taught throughout her New York years: as jazz composition, arranging, trombone and combo faculty at Rutgers University from 2002 to 2004; as adjunct jazz faculty at Western Connecticut State University; as trombone instructor and ensemble coach for the Middle School and Youth Jazz programs at Jazz at Lincoln Center; and, since 2022, as a part-time lecturer at The New School's School of Jazz and Contemporary Music. She also works as an educational specialist for the instrument manufacturer Conn-Selmer.

Weisz's playing carries the imprint of the working Las Vegas show-band trombonists she came up among in the 1980s, above all Carl Fontana, and of a composer's training layered on top of it through her studies with Jim McNeely and Bob Brookmeyer. That combination shows in the range of contexts she moves through without changing character: a big-band section trombonist in Sherrie Maricle's DIVA Jazz Orchestra and in Jimmy Heath's band, an improviser in small groups built around standards and Thelonious Monk repertoire on her own leader dates, and a credited voice in more exploratory settings such as Anthony Braxton's Composition No. 19 (For 100 Tubas). Her original compositions, recognized by the Julius Hemphill Jazz Composition Contest and a BMI Foundation/Charlie Parker Composition Award finalist nod, sit inside a post-bop idiom shaped directly by her teachers rather than by any single stylistic school.