Ocasek met Future Cars Bassist Benjamin Orr in Cleveland in the 1960s after Ocasek saw Orr performing with his band the Grasshoppers on the Big 5 Show, a local musical variety program. He reconnected with Orr a few years later in Columbus, Ohio, and the two began booking bands together. Soon, they formed one of their own and began to perform in and around Ohio State University.

Ocasek grew up in Baltimore, Maryland. When Ocasek was 16 years old, his family moved to Cleveland, Ohio. After graduating from Maple Heights High School in 1963, Ocasek briefly attended Bowling Green State University and Antioch College. However, he dropped out to pursue a career in music.

Ocasek and Orr were in various bands in Columbus and Ann Arbor, Michigan before re-locating to Boston in the early 1970s. In Boston, they formed a Crosby, Stills and Nash-style folk rock band called Milkwood. They released one album, How's the Weather, on Paramount Records in early 1973 but it failed to chart. After Milkwood, Ocasek formed the group Richard and the Rabbits, which included Orr and keyboardist Greg Hawkes, who had played on Milkwood's album. Ocasek and Orr also performed as an acoustic duo during this period. Some of the songs they played became the early Cars songs. Later, Ocasek and Orr teamed up with Guitarist Elliot Easton in the band Cap'n Swing. Cap'n Swing soon came to the attention of WBCN disc jockey Maxanne Sartori, who began playing songs from their demo tape on her show. After Cap'n Swing was rejected by several record labels, Ocasek got rid of the bass player and Drummer and decided to form a band that better fit his style of writing. Orr took over on bass and David Robinson, best known for his career with the Modern Lovers, became the Drummer. Hawkes returned to play keyboards and the band became "The Cars" in late 1976.

Ocasek has been married three times. He married early in life, but divorced and was married to his second wife, Suzanne Otcasek, in 1971. Ocasek was still married to Suzanne when he met model Pavlína Pořízková during filming of the music video for the Cars' song "Drive" in 1984. Ocasek and Porizkova were married in 1989.

The singer released his first solo album in 1982. Beatitude is a somewhat more experimental variation of the Cars' new wave rock sound. On some tracks Ocasek played all of the instruments. Greg Hawkes played on the album. A more synthesizer-heavy follow up, This Side of Paradise, was released in 1986. This featured Hawkes, Elliot Easton and Ben Orr. A No. 15 hit single, "Emotion in Motion," accompanied the album.

Ocasek had a cameo role as a beatnik Painter in the John Waters film Hairspray, and had a small part in the 1987 movie Made in Heaven in which he played a mechanic.

The Cars disbanded in 1988, and Ocasek disappeared from the public eye for a couple of years. He resurfaced in 1990 with his own album, Fireball Zone. One track, "Rockaway," enjoyed a brief stay on the charts, but his solo albums have seen disappointing sales, especially compared to his success with the Cars. He subsequently released other solo works throughout the decade, including 1993's Quick Change World, 1996's Getchertiktz (a collaboration with Suicide's Alan Vega and Canadian poet Gillian McCain comprising only beatnik poetry set to music, sound effects, etc.), and 1997's Billy Corgan-produced Troublizing (which Ocasek supported with a very brief tour, his first since leaving the Cars). In 2005 Ocasek released another album, Nexterday, to little fanfare, but it received positive reviews.

Ocasek has six sons, two from each of his three marriages. His eldest son, Christopher Otcasek, was a singer who formed the rock group Glamour Camp which released one album in 1989. Adam Otcasek was born in 1970. Eron was born in 1973 and Derek was born in 1981.

Ocasek wrote a book of poetry, 1993's Negative Theatre. It was at one time expected to be incorporated into an album and multimedia incarnation of the same name, but those plans were dropped abruptly. For many years Ocasek had a hobby of making drawings, photo collages, and mixed-media art works which, in 2009, were shown at a gallery in Columbus, Ohio as an exhibit called "Teahead Scraps".

He and co-founder of the Cars Benjamin Orr were known to be close friends. Their friendship was commemorated in the song "Silver" which Ocasek wrote as a dedication to Orr upon his death in 2000.

Ocasek stated in a 2005 interview in Rockline that he hated touring and it was unlikely that he would do so again. He also stated he would not be reuniting with the Cars again, but gave the okay to his former bandmates to do so with Todd Rundgren replacing him on vocals as the New Cars.

On April 17, 2006, Ocasek appeared on The Colbert Report and volunteered to put Todd Rundgren "on notice". He appeared again on the July 26, 2006, episode to cheers from the audience as he volunteered to lead a commando mission to "rescue" Stephen Jr., the baby eagle at the San Francisco Zoo named after Stephen Colbert. He also appeared again on April 18, 2007, in order to support his wife during her appearance on the show, after remarks that she found Colbert "extremely attractive". He has been mentioned many times in other episodes as well.

The Cars, with Ocasek, appeared on The Colbert Report on August 9, 2011, to promote their new album, Move Like This.

In 2012, Ocasek wrote another book, "Lyrics and Prose", a complete collection of lyrics from his solo albums, as well from the Cars' albums. It also contains prose and poetry never set to music, also photographs and artwork done over the years that was previously unpublished.