Joseph Salvatore Lovano was born December 29, 1952, in Cleveland, Ohio, to Sicilian-American parents whose families came from Alcara Li Fusi and Cesarò. His father, Tony "Big T" Lovano, was a barber by day and a big-toned tenor saxophonist by night, and he exposed his son to jazz from the start, teaching him standards and how to lead a working gig. Lovano started on alto saxophone at six and switched to tenor at eleven, drawn early to John Coltrane, Dizzy Gillespie and Sonny Stitt. After graduating from Euclid High School in 1971, he enrolled at Berklee College of Music, studying under Herb Pomeroy and Gary Burton; the school awarded him an honorary doctorate of music in 1998.

After Berklee, Lovano worked with organist Jack McDuff and Lonnie Smith before spending three years touring in Woody Herman's big band. He then settled in New York City and joined Mel Lewis's Monday-night big band at the Village Vanguard, developing the ability to play lines with the rhythmic punch of an entire horn section that would mark his later writing. In the mid-1980s he began two of the defining associations of his career: a quartet with guitarist John Scofield, and, more lastingly, a chordless trio with guitarist Bill Frisell led by drummer Paul Motian, documented on the ECM albums Psalm (1982) and It Should've Happened a Long Time Ago (1985) and, after the group moved to the JMT label, Monk in Motian (1988), a Thelonious Monk tribute that added a second saxophonist, Dewey Redman, and pianist Geri Allen. Lovano's own recording career as a leader began during the same years on the Italian label Soul Note, first with the quartet date Tones, Shapes and Colors (1985) and then the quintet session Village Rhythm (1989), which paired him with trumpeter Tom Harrell, pianist Kenny Werner, bassist Marc Johnson and Motian on drums.

Lovano signed to Blue Note Records in 1990 and spent the next two decades building one of the label's deepest contemporary catalogs. Landmarks (1991), produced by Lovano and Scofield, was followed by From the Soul (1992), a quartet date with pianist Michel Petrucciani, bassist Dave Holland and drummer Ed Blackwell, and Universal Language (1993), a sextet session with bassist Charlie Haden, drummer Jack DeJohnette and bassist Steve Swallow doubling on electric bass. Tenor Legacy (1994) paired him in a two-tenor frontline with the younger Joshua Redman, and Rush Hour (1995), arranged and conducted by the composer and historian Gunther Schuller across settings ranging from unaccompanied solo to full orchestra, earned a Grammy nomination. Quartets: Live at the Village Vanguard (1995), recorded across two nights with two different rhythm sections, won DownBeat's Jazz Album of the Year. Trio Fascination: Edition One (1998) reunited him with Holland alongside drummer Elvin Jones, and Friendly Fire (1999) was a co-led session with fellow saxophonist Greg Osby.

The 2000s brought Lovano's first Grammy Award, for 52nd Street Themes (2000), a nonet recording of bebop-era repertoire by Tadd Dameron, Charlie Parker and Monk that won Best Large Jazz Ensemble Album in 2001. He recorded four albums with the veteran pianist Hank Jones, including I'm All For You (2004) and Joyous Encounter (2005), both trios completed by bassist George Mraz and Motian on drums, and Kids: Live at Dizzy's Club Coca-Cola (2007). In the same period he co-founded the Saxophone Summit with Michael Brecker and Dave Liebman, touring and recording together until Brecker's death in 2007, after which Ravi Coltrane took the third chair; he also recorded Oh! (2003) as part of the collective quartet ScoLoHoFo with Scofield, Holland and drummer Al Foster, and toured with the SFJAZZ Collective.

In 2008 Lovano formed the quintet Us Five, with bassist Esperanza Spalding, pianist James Weidman and two drummers, Francisco Mela and Otis Brown III, a lineup built around the two-drummer configuration he described as adding "this other element of creativity." Folk Art (2009) introduced the band, Bird Songs (2011) was a tribute to Charlie Parker, and Cross Culture (2013), the band's last studio album, added guitarist Lionel Loueke as a guest and bassist Peter Slavov alongside Spalding. His own Blue Note run closed three years later with Classic! Live at Newport, taped at the 2005 festival with Hank Jones and issued in 2016 as his twenty-fifth album for the label. Throughout his career Lovano has frequently recorded and performed with his wife, vocalist Judi Silvano.

Since the mid-2010s Lovano has co-led the quintet Sound Prints with trumpeter Dave Douglas, a band formed to write original music in the spirit of Wayne Shorter rather than covering him directly, documented on Sound Prints: Live at Monterey Jazz Festival (2015) and Scandal (2018). He has also moved his own leader work to ECM, forming Trio Tapestry with pianist Marilyn Crispell and drummer Carmen Castaldi for an ongoing trilogy: Trio Tapestry (2019), Garden of Expression (2021) and Our Daily Bread (2023). He has continued to record widely as a guest, including on Polish pianist Marcin Wasilewski's Arctic Riff (2020) and Homage (2025). He has held the Gary Burton Chair in Jazz Performance at Berklee College of Music since 2001 and has been a founding faculty member of the college's Global Jazz Institute since 2009, teaching students including saxophonists Jeff Coffin and Melissa Aldana. He has played Borgani saxophones since 1991 and exclusively since 1999, with a signature Borgani-Lovano model. In 2023 he was the subject of the documentary Lovano Supreme, directed by Franco Maresco, which follows him on a journey to his father's and mother's home towns in Sicily.

Lovano's tenor sound descends from the Coltrane and Sonny Rollins lineage but resists easy placement in any single era: he moves comfortably between hard bop, free improvisation and orchestral writing, often within the same album, and plays a working arsenal of secondary horns, including alto clarinet, the Hungarian double-reed tárogató and Aulochrome, a double soprano saxophone. His time in Paul Motian's drummerless-chords trio shaped an approach built on space and implication rather than fixed harmonic anchoring, an instinct that carried into his own chamber-scaled ECM trio decades later. As a bandleader he has repeatedly built ensembles around unconventional configurations, from the two-drummer Us Five to nonet and orchestral dates arranged with Gunther Schuller, and as a writer he draws as often on bebop repertoire and tributes to Parker and Monk as on his own original compositions.