Biréli Lagrène was born September 4, 1966, in Soufflenheim, a town in the Bas-Rhin department of Alsace, into a Manouche (Sinti) family in which the guitar had already passed down two generations: his father, Fiso Lagrène, and his grandfather were both working guitarists in the Django Reinhardt tradition, and his older brother Gaïti Lagrène played rhythm guitar behind him on his earliest recordings. Biréli began on guitar at around age four under his father's instruction and was performing publicly as a prodigy well before his teens, drawing early attention at gypsy-jazz festivals in Alsace and Germany. His recorded debut, cut live at the Krokodil club in Kirchheim unter Teck on May 29-30, 1980, and released as Routes to Django, announced a teenager who had already absorbed Reinhardt's vocabulary note for note; a second album, the studio-and-live compilation 15 (Fifteen), followed in 1982.

In 1979 Lagrène met violinist Stéphane Grappelli, Reinhardt's own former musical partner, and played for him informally before being invited to sit in on stage, an early validation from the one musician best placed to grant it. Through the early 1980s Lagrène toured and shared bills with a wider circle of visiting guitarists, including Al Di Meola, Larry Coryell and John McLaughlin, later documented together on the 1990 concert film The Super Guitar Trio and Friends. In 1984 he appeared at a Django Reinhardt tribute concert at Fat Tuesday's in New York alongside Coryell and guitarist Vic Juris, billed under the short-lived Biréli Lagrène Ensemble name. The following year he met bassist Jaco Pastorius in New York; the two toured Europe together in 1986 and that same year recorded the duo album Stuttgart Aria, one of Pastorius's last studio sessions before his 1987 death.

Signed to Blue Note in the second half of the 1980s, Lagrène pushed decisively away from pure gypsy jazz into electric fusion, absorbing the vocabulary of Wes Montgomery, George Benson and Jimi Hendrix on Inferno (1987) and Foreign Affairs (1988), both cut in New York with American session players including drummers Dave Weckl and Bernard Purdie. Acoustic Moments (1990) pulled back toward an unplugged setting, and Standards (1992) turned toward straight-ahead jazz outright, a trio date with bassist Niels-Henning Ørsted Pedersen and drummer André Ceccarelli built entirely from the American songbook. My Favorite Django (1995) closed the decade by returning deliberately to Reinhardt's own repertoire, the clearest sign yet that Lagrène meant to keep moving between his two idioms rather than choosing one.

The turn of the millennium brought some of Lagrène's most acclaimed work in small, intimate formats: Duet (1999), a two-guitar record with Sylvain Luc, and Front Page (2000), a power trio with electric bassist Dominique Di Piazza and drummer Dennis Chambers that won the Victoires de la Musique Jazz award in 2001. In 2001 he launched the Gipsy Project, an acoustic ensemble with bassist Diego Imbert, guitarist Hono Winterstein and violinist Florin Niculescu built specifically to revisit Reinhardt's Quintette du Hot Club de France repertoire, and the group's self-titled debut and its several sequels (Gipsy Project & Friends, 2002; Move, 2005; Djangology, 2006, with the WDR Big Band) occupied much of the decade. In 2012 Lagrène was invited to join violinist Jean-Luc Ponty's 50th-anniversary celebration in a trio with bassist Stanley Clarke; the on-stage chemistry led the three to reconvene for the 2015 studio album D-Stringz on Impulse!, alongside the more traditionally post-bop quartet session Mouvements, recorded the same era with saxophonist Franck Wolf and organist Jean-Yves Jung. Lagrène was named a Chevalier des Arts et des Lettres in 2012. His later output has continued to move between poles: Storyteller (2018), a trio session with bassist Larry Grenadier and percussionist Mino Cinélu; Solo Suites (2022), his first fully solo studio album, which closes with a duet featuring his daughter, singer Zoé Lagrène; and Biréli Lagrène Plays Loulou Gasté (2023), a solo-guitar tribute to the French film composer.

Lagrène's playing is built on two distinct, fully mastered vocabularies rather than a single style. On acoustic guitar he works directly in Django Reinhardt's Manouche idiom, all rapid single-line runs, tremolo picking and the driving "la pompe" rhythm technique, executed with a speed and harmonic sophistication that has made him one of the style's most technically complete living players. On electric guitar, beginning with his teenage exposure to Wes Montgomery, John McLaughlin, Larry Coryell and Jimi Hendrix, he plays a harder-edged, funk- and rock-inflected jazz fusion, and in between the two he is a fluent, swinging straight-ahead soloist on jazz standards, equally comfortable in a piano-less trio or an organ quartet. Guitarist John McLaughlin has called him a "guitar phenomenon," and critics have consistently framed his career less as a single evolving style than as a musician who simply declines to be limited to the Reinhardt-tribute role his teenage records seemed to predict, moving between gypsy jazz, fusion and post-bop from album to album and often within the same year.