Like many jazz pianists, Hancock started with a classical music education; Hancock studied from age seven. His talent was recognized early, and he played the first movement of Mozart's Piano Concerto No. 5 in D Major at a young people’s concert with the Chicago Symphony at age eleven. Through his teens, Hancock never had a jazz teacher. Instead, around college age, Hancock grew to like jazz after hearing some Oscar Peterson and George Shearing recordings, which he transcribed on his own time, and which developed his ear and sense of harmony. Hancock also listened to other pianists, including McCoy Tyner, Wynton Kelly and Bill Evans, and studied recordings by Miles Davis, John Coltrane and Lee Morgan. After Hancock spent three and a half years studying musical composition at Grinnell College, Donald Byrd hired Hancock in 1961. (He later received a double major in music and electrical engineering from Grinnell in 1971.) The pianist quickly earned a reputation, and played subsequent sessions with Oliver Nelson and Phil Woods. He recorded his first solo album Takin' Off for Blue Note Records in 1962. "Watermelon Man" (from Takin' Off) was to provide Mongo Santamaria with a hit single, but crucially Takin' Off was to catch the attention of Miles Davis, who was at that time assembling a new band.

Hancock received considerable attention when, in 1963, he joined Miles Davis's "second great quintet". This new band was basically Miles Davis surrounded by fresh, new talent. Davis personally sought out Hancock, who he saw as one of the most promising talents in jazz. The rhythm section Davis organized was young but effective, comprising bassist Ron Carter, seventeen year old drummer Tony Williams, and Hancock on piano. After George Coleman and Sam Rivers each taking turns at the saxophone spot, the quintet would gel with Wayne Shorter on tenor saxophone. This quintet is often regarded as one of the finest jazz ensembles, and the rhythm section has been especially praised for their innovation and flexibility. The second great quintet is the place where Hancock found his own unique voice as a master of jazz piano. Not only did he find new ways to use common chords, he also popularized chords then-rarely used in jazz. Hancock also developed a unique taste for "orchestral" accompaniment with stark contrasts then unheard of in jazz (listen to one of the famous live versions of "My Funny Valentine" recorded by the quintet). With Williams and Carter he would weave a labyrinth of rhythmic intricacy on, around and over existing melodic and chordal schemes. In the later half of the sixties their approach would be so sophisticated and unorthodox that conventional chord changes would hardly be discernable, hence their improvisational concept would somewhat inaccurately be called "Time, No Changes". Maiden Voyage (1965) While in the Davis band, Hancock also found time to record dozens of sessions for the Blue Note label, both under his own name and as a sideman with other musicians such as Wayne Shorter, Tony Williams, Grant Green, Bobby Hutcherson, Sam Rivers, Donald Byrd, Kenny Dorham, Hank Mobley, Lee Morgan and Freddie Hubbard. His albums Empyrean Isles (1964) and Maiden Voyage (1965) were to be two of the most famous and influential jazz LPs of the sixties, winning praise for both their innovation and accessibility (the latter demonstrated by the subsequent enormous popularity of the Maiden Voyage title track as a jazz standard, and by the jazz rap group US3 having a hit single with "Cantaloupe Island" from Empyrean Isles some twenty five years later). Empyrean Isles featured the Davis rhythm section of Hancock, Carter and Williams with the addition of Freddie Hubbard on trumpet, while Maiden Voyage also added former Davis saxophonist George Coleman. Hancock also recorded several less-well-known but still critically acclaimed albums with larger ensembles - My Point of View (1963), Speak Like A Child (1968) and The Prisoner (1969) featured flugelhorn, alto flute and bass trombone. 1963's Inventions and Dimensions was an album of almost entirely improvised music, teaming Hancock with bassist Paul Chambers and two Latin percussionists, Willie Bobo and Osvaldo Martinez. During this period, Hancock also composed the score to Michelangelo Antonioni's film Blow-Up which was to be the first of many soundtracks he would record in his career. By the end of his tenure with Davis, the trumpeter began incorporating elements of rock and popular music into his recordings. Despite some initial reluctance, at Davis's insistence Hancock began doubling on electric keyboards including the Fender Rhodes electric piano. Hancock adapted quickly to the new instruments and they would be instrumental in his artistic endeavors. In the summer of 1968, Hancock left Davis's band to form his own sextet, although he was formally kicked out under the pretext that he was late coming back from a honeymoon in Brazil. Davis would soon disband his quartet to search for a new sound himself. Despite his departure from the working band, Hancock would continue to appear on Miles Davis records for the next few years; noteworthy appearances include In a Silent Way, A Tribute to Jack Johnson and On the Corner.