Although Oates's main role in the duo was Guitarist, he also co-wrote many of the Top 10 songs that they recorded, including (with Hall): "Sara Smile" (the song refers to Hall's then-girlfriend, Sara Allen), "She's Gone", and "Out of Touch", as well as (with Allen and Hall): "You Make My Dreams", "I Can't Go for That (No Can Do)", "Maneater", and "Adult Education". He also sang lead vocals on several more singles in the Hot 100, such as "How Does It Feel to Be Back", "You've Lost That Lovin' Feelin'" (a remake of the 1965 song performed by The Righteous Brothers that was written by Phil Spector, Barry Mann and Cynthia Weil), on which Oates shared lead vocals with Hall, and "Possession Obsession" (with Allen & Hall).

In 1966, he recorded his first single, "I Need Your Love," with The Masters for Philadelphia-based Crimson Records. After graduating from North Penn High School in 1966, John enrolled in Temple University in Philadelphia, where he met Daryl Hall, a senior at Temple who was also a professional musician. The two were involved in several college bands, then formed the duo Hall & Oates, and by 1972, they had signed with Atlantic Records. Hall & Oates went on to record 21 albums (to date), which have sold over 80 million units worldwide, making them arguably the most successful duo in pop–rock history. They have scored ten number-one records and over 20 Top 40 hits and have toured the world for decades. Their involvement in the original Live Aid concert and the charity single "We Are the World", both in 1985, established them further as artists. Their influence on modern American pop music and considerable contributions have been acknowledged by numerous contemporary bands, including Gym Class Heroes and The Killers.

In 1983, Oates was asked whether he regretted not pursuing his degree in journalism. He replied that he did not—and admitted that he had in fact never intended to finish it.

In 1986 Oates contributed the song "(She's the) Shape of Things to Come" on the Soundtrack to the 1986 film, "About Last Night". Oates also co-wrote and sang backup on the song "Electric Blue", recorded by the Australian band Icehouse, which was a Billboard Top Ten hit. He also co-wrote, produced and sang duet with the Canadian group The Parachute Club on the 1987 song "Love is Fire" which was a Top 30 hit in Canada.

Oates has been married twice. His first wife was Nancy Hunter, a former model. He and his second wife Aimee Oates have a son, Tanner, who was born in 1996. They reside in Woody Creek, Colorado as well as Nashville, Tennessee.

Despite 30 years as a chart-topping performer and sought-after Producer, Oates did not release a solo album until 2002's Phunk Shui.

Oates took part, along with Jamie Cullum, in the song "Greatest Mistake" by Handsome Boy Modeling School. The song appears on the 2004 album White People.

Oates's second solo album, 1000 Miles of Life, was released on August 23, 2008.

In March 2010, Oates played with the indie rock band The Bird and the Bee as a surprise guest. The show was a medley of The Bird and the Bee songs, as well as classic Hall & Oates. The performance was dedicated to H&O Bassist T-Bone Wolk who died on February 27, 2010.

On October 1, 2011, Margo Rey charted at #24 on Billboard's Adult Contemporary Tracks with the song "Let the Rain", which was co-written by John Oates.

On March 11, 2013, Oates released a new single, "Stand Strong", which he co-wrote with Teddy Morgan. "Stand Strong" is part of Oates's newest project, "Good Road To Follow", a set of original songs that will be released as digital singles, one after the other. In 2015, Oates released Another Good Road, a DVD and Live CD combination via PS Records / Warner Elektra, which also debuted as a television special on Palladia music channel. The DVD was shot live in a recording studio in Nashville, Tennessee, and features rare footage of his home in Woody Creek, Colorado.

His memoir, Change of Seasons (9781250082657), was published on March 28, 2017 by St. Martin's Press.