The group debuted at Cafe Au Go Go in New York City in 1967, opening for Moby Grape; the band was a hit with the audience, who liked the innovative fusion of jazz with psychedelic rock and roll. After signing to Columbia Records, the group released one of the most critically acclaimed albums of the 1960s, Child is Father to the Man. Without any pop-oriented hit singles, though, the album's sales were sluggish. While sales slowly picked up, personality conflicts started tearing apart the band. Colomby and Katz wanted to move Kooper to the organ exclusively and hire a vocalist for the group. With the debut album slowly achieving critical mass, Kooper left the group to become a record producer for Columbia. Randy Brecker and Jerry Weiss also quit, joining Horace Silver's band and Ambergris, respectively.
Colomby and Katz started recruiting singers, considering the still unknown Stephen Stills and Laura Nyro before settling on David Clayton-Thomas, a Canadian singer. Chuck Winfield, Lew Soloff and Jerry Hyman joined soon after to bring the band up to nine total members. Blood, Sweat & Tears, the group's second, self-titled album, was released in 1969. The album was much more pop-oriented and soon hit the top of the charts and won Album of the Year at the Grammy Awards.
Because of the presence of horns and the lack of Al Kooper, Blood, Sweat & Tears had trouble holding onto any sort of countercultural hipness at a time when this was very important. This was compounded by a United States Department of State-sponsored tour of Eastern Europe. Any voluntary association with the government was extremely unpoular at the time, and the band was ridiculed for it. In retrospect, it is now known that the State Department subtly requested the tour in exchange for more amicability on the issue of Clayton-Thomas' visa.
After returning Stateside, the group released Blood, Sweat & Tears 3 but was a critical and popular failure compared to the prior two albums. Compounding the image problems was a decision to play at Caesar's Palace in Las Vegas, Nevada, a notoriously unhip place in an unhip city. Their fourth album did not sell well and Jerry Hyman was replaced by Dave Bargeron. Personality difficulties had split the group in rock and jazz factions with Clayton-Thomas in the middle; he chose to quit to pursue a solo career. He was replaced by Bob Doyle, then Jerry Fisher. Fred Lipsius quit and was replaced by Joe Henderson, then Lou Marini Jr. Dick Halligan was replaced by Larry Willis while George Wadenius joined as a second guitarist. Amidst the personnel changes, a Greatest Hits album was released.
The new group released New Blood but this album did not reestablish an audience. Jim Fielder and Steve Katz quit as the group moved more towards jazz. No Sweat and Mirror Image followed and sold miserably. Personnel changes continued at a breakneck pace, culminating in the return of David Calyton-Thomas and the release of a successful comeback album called New City. Though this reestablished an audience, Columbia Records dropped the group. After this, the group was effectively dead, though there was a brief resurgence in popularity once the old albums came out on CD.