Pasquale Grasso was born October 19, 1988, in Ariano Irpino, in Italy's Campania region, and grew up on a family farm there with chickens, pigs, grapes and olives. His parents loved jazz and classical music without playing themselves; his father recorded Sonny Rollins concerts broadcast on RAI-TV for the family to watch and brought home records by Dexter Gordon, Coleman Hawkins and Don Byas. His older brother, Luigi Grasso, took up saxophone first, and their father bought Pasquale his first guitar when he was five, on the condition that he practice daily. By the time Luigi was eleven and Pasquale was nine, the brothers were already performing together locally.

Grasso studied with the Italian guitarist Agostino Di Giorgio, a former pupil of Chuck Wayne, beginning in the summer of 1997, and Di Giorgio's technique became a lasting foundation. The following summer, at a workshop in Switzerland, the bebop pianist and educator Barry Harris took both Grasso brothers under his wing; over the next several years Pasquale and Luigi became instructors themselves in Harris's traveling workshops across Italy, Switzerland, France, Spain, the Netherlands and Slovenia. In 2008 Grasso earned a degree in classical guitar from the Conservatorio Giovanni Battista Martini in Bologna under Professor Walter Zanetti, later adding a master's degree there, and folded that classical position and technique into the jazz vocabulary he had already absorbed from Di Giorgio and Harris.

Grasso relocated to New York City in 2012 as a jazz ambassador for the U.S. State Department, touring internationally under that program while building a footing in the city's traditional-jazz scene. He became a regular in reedman Chris Byars's quartet, recording on the SteepleChase sideman dates The Music of Duke Jordan (2014), Two Fives (2015), The Music Of Frank Strozier (2017) and New York City Jazz (2018), and in bassist Ari Roland's circle, appearing on saxophonist Zaid Nasser's The Stroller (2017) and bassist Jamale Davis's We Worked In The Bricks (2017) and Workers' Comp (2018), both on Gut String Records. In 2015 he self-released his debut album as a leader, Reflections of Me, a set of Great American Songbook standards and four originals cast as a joint homage to Bud Powell and Art Tatum. That October he won the Wes Montgomery International Jazz Guitar Competition in New York, taking a five thousand dollar prize and performing with guitarist Pat Martino's organ trio.

Grasso signed to Sony Masterworks and, starting in 2019, built a catalog split between unaccompanied solo-guitar records and trio dates with bassist Ari Roland and drummer Keith Balla. The solo series runs from Solo Holiday and Solo Monk (both 2019, the latter on the Okeh imprint) through Solo Standards and Solo Bud Powell (both 2020), Solo Masterpieces and Solo Ballads (both 2021), and Solo Be-Bop! (2025). The trio records, billed under his own name and eventually as the Pasquale Grasso Trio, include Pasquale Plays Duke (2021), a set of Duke Ellington repertoire with guest vocal features from Samara Joy on "Solitude" and Sheila Jordan on "Mood Indigo"; Be-Bop! (2022), a tribute to Dizzy Gillespie and Charlie Parker; and Fervency (2025), produced by Matt Pierson.

Alongside his own leader catalog, Grasso became the regular guitarist behind singer Samara Joy, appearing on her self-titled 2021 debut album and on Linger Awhile (2022, Verve), which won the Grammy Award for Best Jazz Vocal Album at the 65th Annual Grammy Awards in February 2023, with Grasso credited among its musicians. He teaches as a Lecturer of Jazz Studies at SUNY Purchase's Conservatory of Music, has given masterclasses internationally, and has drawn public praise from guitarist Pat Metheny, who called him "the best guitar player I've heard in maybe my entire life."

Grasso is known for a pianistic approach to jazz guitar, built on the harmonic and rhythmic vocabulary of Bud Powell and Art Tatum rather than the guitar lineage most jazz guitarists draw from first. His classical training under Walter Zanetti at the Bologna conservatory gave him a right-hand and left-hand position closer to a classical guitarist's than a typical jazz player's, which he uses to voice full chord-melody arrangements and walking bass lines simultaneously, an approach that let him build an entire recorded catalog of unaccompanied solo-guitar albums. The bebop language underneath it all traces to Barry Harris, whose workshops shaped both Grasso brothers from their teenage years, and to Agostino Di Giorgio's transmission of the guitarist Chuck Wayne's technique. Reviewers and fellow musicians, including Pat Metheny, have singled him out as an unusually complete technician among contemporary jazz guitarists.