Christopher Stephen Botti was born in Portland, Oregon, on October 12, 1962, and raised in Corvallis, with two years of his childhood spent in Italy. His first musical influence was his mother, a classically trained pianist and part-time piano teacher. He started trumpet at nine and committed to it at twelve, after hearing Miles Davis play "My Funny Valentine." In 1981 he was picked for McDonald's All American High School Jazz Band, which gave him his first Carnegie Hall appearance. At seventeen he finished his remaining high school credits at Mount Hood Community College in Gresham, Oregon, scheduling classes around evening gigs in Portland clubs. The college's jazz program, led by Larry McVey, was a regular stop for Stan Kenton and Mel Tormé when they were looking for players, and there Botti played alongside his friend Todd Field, a trombonist who later became an Academy Award nominated filmmaker.

After Crescent Valley High School he studied at the Indiana University School of Music with the jazz educator David Baker and the trumpet professor Bill Adam. Two National Endowment for the Arts grants paid for private study with Woody Shaw and George Coleman over two consecutive summers. He left Indiana in his senior year for short touring stints with Frank Sinatra and Buddy Rich, and in 1985 he moved to New York City to work as a studio musician.

His name was made first as a sideman for pop singers. In 1990 he began a long touring and recording relationship with Paul Simon, and over those years he also performed or recorded with Aretha Franklin, Natalie Cole, Bette Midler, Joni Mitchell, Natalie Merchant, Scritti Politti and Roger Daltrey. On August 15, 1991, he played with Simon in New York's Central Park on the Rhythm of the Saints tour, and the concert was released as Paul Simon's Concert in the Park. On that tour he met Michael Brecker, which led to Botti co-producing "Evocations" on the Brecker Brothers' Out of the Loop. In the late 1990s he was also a member of Bruford Levin Upper Extremities, a more experimental fusion group with Bill Bruford, bassist Tony Levin and guitarist David Torn, which released a self-titled album in 1998 and the live B.L.U.E. Nights in 2000.

His own records began with First Wish (Verve Forecast, February 28, 1995). Midnight Without You (1997) included a collaboration with Paul Buchanan of The Blue Nile, and Slowing Down the World (GRP, 1999) carried vocals by Sting and Jonatha Brooke. He also composed the score for the 1996 film Caught. From 1999 Botti toured as a featured soloist with Sting on the Brand New Day tour, a two-year run that ended with the live CD and DVD All This Time, taped at Sting's Tuscany estate on September 11, 2001. Botti has described his close friendship with Sting as an important development in his career.

Bobby Colomby, the Blood, Sweat & Tears drummer, introduced him to Columbia and became his producer and manager. Night Sessions (2001), which he wrote and produced with the keyboardist Kipper, was the first Columbia release and reached No. 4 on Billboard's jazz albums chart. December (2002), a holiday album, and A Thousand Kisses Deep (2003) also reached the jazz Top 5. When I Fall in Love (September 28, 2004) was the breakthrough: an orchestral ballad record with the London Session Orchestra, guest vocals from Sting and Paula Cole, and a rhythm section that included drummers Vinnie Colaiuta and Billy Kilson. It reached No. 1 on the jazz chart and No. 37 on the Billboard 200 and went Gold. To Love Again: The Duets (October 18, 2005) repeated the formula with guest vocalists Sting, Cole, Michael Bublé, Jill Scott, Paul Buchanan, Gladys Knight, Renee Olstead, Rosa Passos and Steven Tyler, with Christian McBride and Peter Erskine among its bassists and drummers. It reached No. 1 on the jazz chart and No. 18 on the Billboard 200 and also went Gold. Billy Childs, Gil Goldstein and Heitor Pereira won the 2006 Grammy for Best Instrumental Arrangement Accompanying Vocalist(s) for "What Are You Doing the Rest of Your Life?" from that album.

A PBS concert, Live: With Orchestra and Special Guests, followed in 2006 with duets with Sting, Burt Bacharach, Gladys Knight, Jill Scott and Renee Olstead. Italia (September 25, 2007) turned to his Italian roots, with Andrea Bocelli singing the title song, and reached No. 1 on the jazz chart and No. 27 on the Billboard 200. It was nominated for the Grammy for Best Pop Instrumental Album. Chris Botti in Boston, recorded at Symphony Hall on September 18 and 19, 2008, with the Boston Pops Orchestra, came out on CD and DVD on March 31, 2009. Its guests were Yo-Yo Ma, Steven Tyler, Josh Groban, Katharine McPhee, John Mayer and Sting, and the set included the Miles Davis and Bill Evans piece "Flamenco Sketches." It went Platinum in the United States and brought three Grammy nominations at the 2010 ceremony: Best Pop Instrumental Album, Best Instrumental Arrangement for "Emmanuel," and Best Long Form Music Video.

Impressions (April 17, 2012) reached No. 1 on the jazz chart and won the Grammy for Best Pop Instrumental Album on February 10, 2013. Its guests included Herbie Hancock on piano, Mark Knopfler, Vince Gill, Andrea Bocelli and David Foster. Four of his albums have reached No. 1 on Billboard's jazz albums chart: When I Fall in Love, To Love Again, Italia and Impressions. A third PBS concert, Great Performances: The Chris Botti Band in Concert, was released in 2018 with Sy Smith, Veronica Swift, Caroline Campbell, Joey DeFrancesco and Taylor Eigsti. In October 2023 he made his Blue Note debut with Vol. 1, his first studio album in more than a decade, produced by David Foster. Botti has said he wanted to strip away the orchestral arrangements and guests and focus on his own playing and his band's, and the record is a small-group set of standards with the violinist Joshua Bell on "My Funny Valentine," the pianist Taylor Eigsti, the drummer Vinnie Colaiuta and the guitarist Gilad Hekselman. His regular touring band includes bassist Zach Moses, keyboardist Julian Pollack and saxophonist Chad Lefkowitz-Brown. His own site lists concert dates through at least December 2026, and he has held an annual holiday residency at the Blue Note Jazz Club in New York.

Botti is a lyrical, romantic ballad trumpeter, and the pop and smooth-jazz sides of his career are central to it rather than incidental. His first releases are often classified as smooth jazz, AllMusic lists his styles as Contemporary Jazz, Crossover Jazz, Instrumental Pop, Smooth Jazz, Jazz-Pop and Standards, and his sideman career was largely with pop singers: Paul Simon, Sting, Barbra Streisand, Michael Bublé, Rod Stewart, James Taylor and John Mayer among them. His Grammy recognition, one win and four nominations, has come in pop instrumental, arrangement and video categories rather than a jazz category. The critic Alex Henderson, reviewing Slowing Down the World, argued that Botti was capable of a good deal more than the genre's background music.

The jazz link is real and documented. He says he committed to the trumpet at twelve on hearing Miles Davis play "My Funny Valentine." He studied at Indiana University with David Baker and, on NEA grants, with Woody Shaw and George Coleman. AllMusic describes the orchestral approach of When I Fall in Love as influenced by Miles Davis's albums with the arranger Gil Evans, and his 2009 Boston concert included Davis's "Flamenco Sketches." His bands have included jazz players such as Billy Childs, Vinnie Colaiuta and Taylor Eigsti. Vol. 1 on Blue Note, which he presented as a return to small-group acoustic jazz and standards, cites Kind of Blue, John Coltrane and Johnny Hartman, and Pat Metheny and Charlie Haden's Beyond the Missouri Sky as models. His sound is a clear, glowing tone, often with a Harmon mute, played on a large-bore Martin Committee trumpet made in 1939.