After four years with Puente, he was one of the most sought-after percussionists in New York City's thriving music scene. He attended jam sessions with notable artists such as Max Roach, Charlie Parker, Art Blakey and other jazz giants. He also recorded with Sonny Stitt, Lou Donaldson, Red Garland, Gene Ammons, Eddie "Lockjaw" Davis, Cannonball Adderley , Freddie Hubbard, Cal Tjader, Dizzy Gillespie, and others.
Barretto got his first job as a bandleader in 1961 when Orrin Keepnews of Riverside Records, asked him to form a charanga for a recording. Keepnews was familiar with Barretto's jazz work and the collaboration resulted in the album Pachanga With Barretto. This was followed by the Latin jam Latino in 1962, on which Barretto was joined by Jose "Chombo" Silva on the tenor sax and Alejandro "El Negro" Vivar on the trumpet.
In 1962, Barretto released the album Charanga Moderna. The track "El Watusi" reached the Top 20 pop chart in the United States in 1963 and went gold.
His next eight albums between 1963 and 1966 thrashed around in various directions and consistently eluded commercial success. The musical merit of some of his recorded work from this period was not appreciated until years later. His fortunes changed when he signed to Fania Records in 1967. He dropped violins for an all-brass frontline and made the R&B- and jazz-flavoured Acid, which won him major popularity among Latin audiences for the first time.
Barretto's next nine albums on Fania between 1968 and 1975 were increasingly successful. In 1972, with the Ray Barretto Orchestra he recorded the very popular and important album Que Viva La Musica. The following year he records many songs of Cuban composers in the album Indestructible. The only set back was in late 1972 when Adalberto Santiago, his vocalist since 1966, and four other band members, left to found the band "Tipica 73".
Perhaps his masterpiece album, Carnaval, in 1972, included the smash song Cocinando Suave and Summertime. His 1975 album, Barretto, with vocalists Ruben Blades and Tito Gomez was his biggest seller to date. It contained the prize-winning hit "Guarare" and was nominated for a Grammy Award in 1976. He was also voted Best Conga Player Of The Year for 1975 and 1976 in Latin NY magazine annual poll.
Meanwhile, Barretto had tired of gruelling daily nightclub gigs and felt that clubs stifled creativity and gave no room for experimentation. He was also pessimistic that pure salsa could cross over to a wider audience. On New Year's Eve 1975, he played his last date with his salsa band. They continued under the name Guarare and released three albums: Guarare (1977), Guarare (1979) and Onda Tipica (1981).
Barretto went on to organize a fusion-orientated concert band. An agreement was struck between Fania and Atlantic Records and the first release on his new label was Barretto Live: Tomorrow, a two-disc recording of his successful debut concert at the Beacon Theatre, New York in May 1976.
Barretto's 1977 and 1978 albums were his last on Atlantic. However, he still managed to win the Latin NY titles for Musician Of The Year and Best Conga Player Of The Year in October 1977. However, his fusion band turned out to be a commercial flop, as he injured a hand and was unable to play for a while.
In 1979 he went back to Fania and reunited with Adalberto Santiago to produce Rican/Struction, a return to progressive salsa. The album was a smash hit and won him the 1980 Latin NY titles for Album Of The Year, Musician Of The Year and Best Conga Player. Two albums, Giant Force in 1980 and Rhythm of Life in 1982, featured the impressive voice of lead singer, Ray De La Paz (ex-Guarare), and talented young New York-born Latino trombonist, Joe de Jesus.