Spas Wenkoff was born on 23 September 1928 in Veliko Tarnovo.

After practicing as a lawyer for five years while training his voice under I. Josifov in Sofia, Spas Wenkoff trained under Mme. Safirowa in Russia and Johannes Kemter in Dresden.

As early as 1954, he was singing one of the title roles in the Georgian comic opera Keto da Kote by W. I. Dolidse at the Municipal Theater of Veliko Tarnovo.

From 1962 to 1965, he was heard with the ensemble of the Ruse opera house in Bulgaria. Then he became known in East Germany, where he enjoyed great success. He sang at the Dobeln theater from 1965 to 1968, from 1968 to 1971 at the Municipal Theater of Magdeburg, from 1971 to 1975 in Halle an der Saale (where he sang his first Tannhäuser), and in 1975, he was hired as the principal heldentenor at the Berlin State Opera, where he was heard until 1984.

During a 1975 guest engagement at the Dresden State Opera, he scored a particular success as Tristan. He sang the role at the Bayreuth Festival in 1976 and in 1982/83, while adding Tannhäuser.

Having begun his career with the most demanding dramatic parts in the Italian repertoire, in later years he became known as a great Wagner interpreter, appearing as a guest throughout the world. In 1982 he triumphed as Tannhäuser at the Vienna State Opera, where he took over the title role for the suddenly indisposed Reiner Goldberg.

In 1981, he answered a call to the Metropolitan Opera, where he made his debut as Tristan. From 1984, he appeared mainly at the Deutsche Oper Berlin, at the State Operas of Vienna and Munich and at the Cologne opera.

In 1987, he appeared at the Bern Municipal Theater and at the Vienna State Opera as Tannhäuser. In 1990, he was a guest artist in Cologne; in 1991 he appeared in Vienna as Tristan and at Covent Garden as Siegfried in Götterdämmerung.

His older brother Wenko Wenkoff (1921–92) was also a well-known tenor. Spas Wenkoff spent his final years in Bad Ischl in the Upper Austrian countryside, where he died on 12 August 2013.