When Gaye signed with Tamla, he pursued a career as a performer of jazz music and standards, having no desire to become an R&B performer. Before the release of his first single, Gaye started spelling his surname with added "e", in the same way as did Sam Cooke. Author David Ritz wrote that Gaye did this to silence rumors of his sexuality, and to put more distance between himself and his father.

Marvin helped shape the sound of Motown in the 1960s, first as an in-house session player and later as a solo artist with a string of successes, which earned him the nicknames "Prince of Motown" and "Prince of Soul". In 1962, Gaye found success as co-writer of the Marvelettes track "Beechwood 4-5789", on which he also played drums. His first solo success, "Stubborn Kind of Fellow", was later released that September, reaching No. 8 on the R&B chart and No. 46 on the Billboard Hot 100. Gaye first reached the pop top 40 with the dance song, "Hitch Hike", peaking at No. 30 on the Hot 100. "Pride and Joy" became Gaye's first top ten single after it's release in 1963. The three singles and songs from the 1962 sessions were included on Gaye's second album, That Stubborn Kinda Fellow, released on Tamla in January 1963. Starting in October 1962, Gaye performed as part of the Motortown Revue, a series of concert tours headlined at the north and southeastern coasts of the United States as part of the Chitlin' Circuit, a series of rock shows performed at venues that welcomed predominantly black musicians. A filmed performance of Gaye at the Apollo Theater took place in June 1963. Later that October, Tamla issued the live album, Marvin Gaye Recorded Live on Stage. "Can I Get a Witness" became one of Gaye's early international successes. In 1964, Gaye recorded a successful duet album with singer Mary Wells titled Together, which reached No. 42 on the pop album chart. The album's two-sided single, including "Once Upon a Time" and 'What's the Matter With You Baby", each reached the top 20. Gaye's next solo success, "How Sweet It Is (To Be Loved By You)", which Holland-Dozier-Holland wrote for him, reached No. 6 on the Hot 100 and reached the top 50 in the UK. Gaye started getting television exposure around this time, on shows such as American Bandstand. Also in 1964, he appeared in the concert film The T.A.M.I. Show. Gaye had two number-one R&B singles in 1965 with the Miracles-composed "I'll Be Doggone" and "Ain't That Peculiar". Both songs became million-sellers. After this, Gaye returned to jazz-derived ballads for a tribute album to the recently-deceased Nat "King" Cole. After recording "It Takes Two" with Kim Weston, Gaye began working with Tammi Terrell on a series of duets, mostly composed by Ashford & Simpson, including "Ain't No Mountain High Enough", "Your Precious Love", "Ain't Nothing Like the Real Thing" and "You're All I Need to Get By". In October 1967, Terrell collapsed in Gaye's arms during a performance in Farmville, Virginia. Terrell was subsequently rushed to Farmville's Southside Community Hospital, where doctors discovered she had a malignant tumor in her brain. Gaye's Motown songs include "Ain't That Peculiar", "How Sweet It Is (To Be Loved by You)", and "I Heard It Through the Grapevine". He also recorded duets with Mary Wells, Kim Weston, Tammi Terrell, and Diana Ross. During the 1970s, Gaye recorded the albums What's Going On (1971) and Let's Get It On (1973) and became one of the first artists in Motown to break away from the reins of a production company. His later recordings influenced several R&B subgenres, such as quiet storm and neo soul. "Sexual Healing", released in 1982 on the album Midnight Love, won him his first two Grammy Awards. Gaye's last televised appearances were at the 1983 NBA All-Star Game, where he sang "The Star-Spangled Banner"; and on Motown 25: Yesterday, Today, Forever; and Soul Train. This concert recording was made several months before his untimely death.