Joseph Lepore was born in New York City in 1967 and raised in Salerno, on the Tyrrhenian coast south of Naples, after his Italian parents moved the family back to their home country. His training was classical: he graduated from the conservatory in Salerno with high honors, and not long afterward left for Rome and the jazz scene there. He holds both American and Italian citizenship, and for the whole of the 1990s he worked as an Italian bassist.

Rome put him in front of visiting Americans as well as the Italian players. The list he gives of the musicians he worked with in those years runs to Bob Dorough, Antonio Faraò, Roberto Gatto, Joy Garrison, George Garzone, Steve Grossman, Tom Kirkpatrick, Dave Liebman, Mike Mainieri, Bob Mover, Romano Mussolini, Jimmy Owens, Enrico Pieranunzi, Tony Scott, Gary Smulyan and Eliot Zigmund. He also played on Italian television and taught jazz bass performance and theory in music schools in both Salerno and Rome. His first appearance on record is a single track of the guitarist Nicola Mingo's Modern Age (Penta Flowers, 1996), where Dario Deidda holds the bass chair for the rest of the album; the hard-bop group Blue Messengers, whose self-titled record came out on Baol Music in 1997, was his first regular band on disc.

From 1997 to 1999 he played in the quartet of the alto saxophonist Rosario Giuliani, with Pietro Lussu on piano and Lorenzo Tucci on drums. That band took first prize out of sixty entrants at the Europ Jazz Contest in Brussels in September 1997, and three of its performances were issued on the contest's own compilation the following year. The quartet recorded twice for Philology, Flashing Lights and Connotazione Blue, and worked the European festival circuit: Getxo in Bilbao, Jazz à Liège, Umbria Jazz in Perugia, Jazz & Image in Rome, Ancona, Marajazz, Urbino and Teano. Lepore also recorded with the pianist Fausto Ferraiuolo on Guajon (Dischi Della Quercia, 1999). Around the same time he took a small on-screen part in Anthony Minghella's The Talented Mr. Ripley.

He moved back to New York in 1999 and landed immediately in a steady job, playing bass in Trio 65, the house band at the Rainbow Room on the sixty-fifth floor of Rockefeller Center, six nights a week, with Ehud Asherie on piano and Tommaso Cappellato on drums. The trio's album of Billy Strayhorn material came out on NuJazzCity in 2000. Steady work in the New York rooms followed, most of it at Smalls and Mezzrow in the West Village, where the club's archive documents him on more than three hundred and forty sets since December 2007. In 2004 he toured Africa with the singer Cynthia Scott as part of the State Department and Kennedy Center's American Music Abroad programme, returned in 2007 with the trumpeter Charlie Porter's quartet, and accepted a teaching grant that took him to the École Nationale de Musique in Abidjan, Ivory Coast. In 2006 he had gone back to school himself, entering the jazz programme at City College of New York, where John Patitucci was among his teachers.

The turn came in 2008, when Greg Osby picked him for the band of younger players he was assembling around his new label, Inner Circle Music. Lepore is the bassist on Osby's 9 Levels (Inner Circle Music, 2008), alongside Adam Birnbaum, Nir Felder, Hamir Atwal and Sara Serpa, and the association led directly to a record of his own. On December 4 and 5, 2008 he took a quartet into Indaba Studio in Whitestone, Queens and cut Journal, eight of his own compositions, which he also arranged and produced. The band was Lance Murphy on tenor saxophone, Tim Collins on vibraphone and Nasheet Waits on drums, an unusual front line for a bass-led date in that it has no piano at all. The tapes were mixed and mastered at Systems Two in Brooklyn in September and October 2009 and the album appeared on Inner Circle Music in August 2010, with a CD following in November. Reviews were warm and prompt: Raul Amador in Bass Musician Magazine in October 2010, Bill Milkowski in JazzTimes on November 1, and Mark Corroto at All About Jazz the following April, who heard Bobby Hutcherson in Collins's vibraphone playing and Thelonious Monk in the writing. John Patitucci and Marc Copland both supplied endorsements.

The years since have been busy and almost entirely spent in other people's bands. He is the bassist on Shauli Einav's Opus One (Plus Loin Music, 2011), the Israeli saxophonist's New York record, with Shai Maestro on piano, Johnathan Blake on drums and Andy Hunter on trombone. In late 2010 he began hosting jam sessions at his own apartment with the saxophonist Eric Person and the drummer Shinnosuke Takahashi; the three formalised the group as TrioKinesis in 2011 and recorded a twelve-track self-titled album at Thunderball Studio in Brooklyn in April 2012, released that June, with one Lepore original, "Not Yet," among tunes by Person, Joe Henderson and Wayne Shorter. The same year brought Melissa Aldana's Second Cycle on Inner Circle Music and the London pianist Jonathan Gee's Dragonfly, a trio date with Waits that grew out of a partnership begun in 2007. He recorded Where or When with the Italian saxophonist Emanuele Cisi in 2013, studied with Ron Carter through 2013 and 2014, and worked with the guitarist Paul Bollenback from 2012 to 2015, recording Portraits in Space and Time in 2014.

Since 2015 he has held the bass chair in a saxophone, bass and drums trio with Tim Armacost and Michael Petrosino, a piano-less format he keeps returning to. The trio toured Sudan in December 2017, giving workshops as well as concerts, and named the record it released in October 2019 Khartoum. He plays throughout the baritone saxophonist Adison Evans's Meridian (2018), a session that also uses Roberto Giaquinto on drums, Silvano Monasterios on piano and Troy Roberts on tenor. His longest-standing current association is with the trombonist David Gibson, whose quartet he has anchored at Smalls, Mezzrow and Jazzcultural for a decade and whose Fellowship (Imani Records) he recorded with Davis Whitfield and Kush Abadey under Orrin Evans's production. He continues to lead occasional nights under his own name, and he was the bassist on the singer Muffy Styler's 2024 recording of Al Cohn's "Night Bird," with Joe Cohn on guitar.

Lepore is a supporting bassist with a composer's ear, and the two halves show up in different places. As a player he is described consistently in the same terms across two decades of endorsements and reviews: warm, fluid, unhurried, and reliable in the strict sense that the pulse does not move. Patitucci, who taught him at City College, called the tone warm and very fluid; Marc Copland described the imagination and the composing skill in the same breath. Reviewing Journal, Mark Corroto called it a solid and reliable recording with a consistent and upright sound and noted that Lepore never neglects the groove, while Bill Milkowski heard hip, insistently swinging grooves and filed the record as neo-bop. The choice of instrumentation on his own dates tells the rest. Journal is a quartet with no piano, so the bass and the vibraphone share the harmonic job between them, and the Armacost trio removes the chordal instrument altogether. That is a format where a bassist has nowhere to hide, and it is the one he has kept coming back to since 2015.

His writing is more openly programmatic than his playing. Each of the eight pieces on Journal has a stated source: "Running" from the pace of modern life, "Waiting for Better Times" written while a broken ankle healed, "Sphere's" from a long admiration for Thelonious Monk, "The Lazy One" as a first experiment in 5/4, "The Big Apple" as a dedication to New York, "The Vampire" from the Anne Rice novel his partner was reading, and "Drawing Hands" from the Escher lithograph. He noted at the time that the whole set came out of his years in Italy rather than his years in New York, which had produced a long stretch of writer's block. The Italian training also shows in the range he can cover: he moves between Neapolitan hard bop, the mainstream repertory that the Rainbow Room job required six nights a week, and the freer trio playing of the Armacost group without visibly changing his approach.