Terrell and Gaye's first major hit was the Nick Ashford and Valerie Simpson composition, "Ain't No Mountain High Enough". The duo quickly followed up with the top five hit ballad, "Your Precious Love". Despite rumors of a romantic relationship – Gaye was married to Anna Gordy and Terrell was dating Temptations lead vocalist David Ruffin – both singers denied such a relationship with Gaye saying later that they had a brother-and-sister relationship, a statement reiterated by Ashford & Simpson. Other hit singles the duo scored within an eighteen-month period included "If I Could Build My Whole World Around You", "Ain't Nothing Like the Real Thing" and "You're All I Need to Get By". Other hits such as "You Ain't Livin' till You're Lovin'" and "The Onion Song" found success in Europe. The duo's recording of "If This World Were Mine", the b-side of "If I Could Build My Whole World Around You", found modest success on the charts, the first sole Gaye composition to do so. The song later found major R&B success when Luther Vandross covered it with Cheryl Lynn over a decade later.
The duo was also a success together onstage, Terrell's easy-going nature with the audience contrasting from Gaye's laid-back approach. However, that success was short-lived. On October 14, 1967, while performing at Virginia's Hampden-Sydney College, Terrell collapsed in Marvin's arms. She had been complaining of headaches in the weeks leading up to the concert, but had insisted she was all right. However, after she was rushed to Southside Community Hospital, doctors found that Terrell had a malignant brain tumor.
The diagnosis ended her performing career, though she still occasionally recorded, often with guidance and assistance. Terrell ceased recordings in 1969 and Motown struggled with recording of a planned third Gaye and Terrell album. Gaye initially had refused to go along with it saying that he felt Motown was taking unnecessary advantage of Terrell's illness. Gaye only reluctantly agreed because Motown assured him recordings would go to insure Terrell's health as she continued to have operations to remove the tumor, all of which were unsuccessful. In September 1969, the third Gaye and Terrell duet album, Easy was released, with many of the songs saaid to have been subbed by Valerie Simpson,