The child of a physician in Niterói, Brazil, Mendes attended the local conservatory with hopes of becoming a classical pianist. As his interest in jazz grew, he started playing in nightclubs in the late-1950s just as bossa nova, a jazz-inflected derivative of samba, was taking off. Mendes played with Antonio Carlos Jobim (regarded as a mentor) and many U.S. jazz musicians who toured Brazil.
Mendes formed the Sexteto Bossa Rio and recorded Dance Moderno in 1961. Touring Europe and the United States, Mendes recorded albums with Cannonball Adderley and Herbie Mann and played Carnegie Hall. Mendes moved to the U.S. in 1964 and cut two albums under the Brasil '65 group name with Capitol Records and Atlantic Records.

When sales were tepid, he replaced his Brazilian born vocalist Wanda de Sa with the distinctive voice of Chicago native Lani Hall (who learned Mendes' Portuguese material phonetically), switched to Herb Alpert's A&M label, and released Herb Alpert Presents Sergio Mendes and Brasil '66, an album that went platinum based largely on the success of the single "Mas Que Nada" (a Jorge Ben cover) and the personal support of Alpert, with whom Mendes toured regularly.

The original lineup of Brasil '66 was Mendes (piano), vocalists Lani Hall and Janis Hansen, Bob Matthews (bass), Jose Soares (percussion) and Joao Palma (drums). John Pisano guested as guitarist. This line-up recorded three albums between 1966-1968 (including the best-selling Look Around LP), before there was a major personnel change for their fourth album Fool on the Hill.

Karen Philipp replaced Hansen as the second female vocalist, while veteran drummer Dom Um Romao teamed with Rubens Bassini to assume percussionist duties. Sebastiao Neto was the new bassist and Oscar Castro-Neves the guitarist. This line up had a more orchestrated and big band sound than their predecessors. Most significantly, in the early 1970s, lead singer Hall pursued a solo career and became Alpert's second wife. Some accounts claim that Mendes was upset with Alpert for years for "stealing" Hall away from his group.

Though his early singles with Brasil '66 (most notably "Mas Que Nada") met with some success, Mendes really burst into mainstream prominence when he performed the Oscar nominated Burt Bacharach and Hal David song "The Look of Love" on the Academy Awards telecast in April 1968. Brasil '66's version of the song quickly shot into the top 10, peaking at #4 and eclipsing Dusty Springfield's version from the soundtrack of the movie, Casino Royale. Mendes spent the rest of 1968 enjoying consecutive top 10 and top 20 hits with his follow-up singles, "The Fool on the Hill" and "Scarborough Fair." From 1968 on, Mendes was arguably the biggest Brazilian star in the world, enjoying immense popularity worldwide and performing in venues as varied as stadium arenas and the White House, where he gave concerts for both Presidents Lyndon B. Johnson and Richard Nixon.

Mendes' career in the U.S. stalled in the mid-1970s, but he remained very popular in South America and Japan. His two albums with Bell Records in 1973 and 1974, followed by several for Elektra from 1975 on, found Mendes continuing to mine the best in American pop music and post-Bossa writers of his native Brazil, while forging new directions in soul with collaborators like Stevie Wonder, who wrote Mendes' R&B-inflected minor hit, "The Real Thing."

In 1983, he rejoined Alpert's A&M records and enjoyed huge success with a self-titled album and several follow-up albums, all of which received considerable adult contemporary airplay with charting singles. "Never Gonna Let You Go", featuring vocals by Joe Pizzulo and Leza Miller, equalled the success of his 1968 single "The Look of Love" by reaching #4 on the Billboard Hot 100 chart; it also spent four weeks atop the Billboard adult contemporary chart. In 1984, Mendes worked with singer Lani Hall again.

By the time Mendes released his Grammy-winning Elektra album Brasileiro in 1992, he was the undisputed master of pop-inflected Brazilian jazz. The late-1990s lounge music revival brought retrospection and respect to Mendes' oeuvre, particularly the classic Brasil '66 albums. His stature in his native Brazil is reflected by "Cantor de Mambo," a song by fellow Brazilians Os Mutantes, which they regularly dedicate to Mendes in concert.

Timeless features a wide array of neo-soul and alternative hip hop guest artists, most prominently will.i.am and The Black Eyed Peas. It was released February 14, 2006 by Concord Records.

It features The Black Eyed Peas, Erykah Badu, Black Thought, Chali 2na of Jurassic 5, India.Arie, John Legend, Justin Timberlake, Q-Tip, Stevie Wonder and Pharoahe Monch.

The 2006, re-recorded version of "Mas que Nada" with The Black Eyed Peas had additional vocals by Gracinha Leporace (Mendes' wife); a version that is included on his album Timeless. In Brazil, the song is pretty well-known for being the theme song for the local television channel Globo's Estrelas.

The Black Eyed Peas' version also contains a sample of their 2004 hit "Hey Mama". The re-recorded song became popular on many European charts. On the UK Singles Chart, the song entered at #29 and rose to and peaked at #6 on its second week on the chart.