Born in Kalamazoo, Michigan, he reportedly began studying piano at the age of four. He attended the Curtis Institute and the Julliard School. At age 20, he made his Broadway debut conducting Gian Carlo Menotti's opera The Consul at its New York premier. He made his debut at the New York City Opera at age 21, and he became the second youngest conductor at age 25 to debut at the Metropolitan Opera.

He was awarded a Tony in 1955 for his musical direction of the play, The Saint of Bleecker Street. In 1958, Thomas conducted the first open air concert at the Italy's Spoleto Festival of Two Worlds, founded by his mentor and friend Menotti, with Thomas.

He also conducted the ill-fated premiere of Samuel Barber's Antony and Cleopatra (1966), written to celebrate the opening of the Metropolitan Opera's new home in Lincoln Center. At one time he was named as one of the 100 most important men in America.

Thomas was appointed Distinguished Professor of Music and was a member of the College-Conservatory of Music (CCM) faculty from 1972 to 1977.

He was a regular conductor with the New York Philharmonic and the Chicago Symphony Orchestra, and made recordings with them, but in 1970 he finally took a full time orchestral position with the Cincinnati Symphony Orchestra, succeeding his predecessor at the Metropolitan Opera, Max Rudolf, a position he held until his career was tragically cut short by his suddent death of lung cancer at age 47. He is buried in Italy.

Schippers' spectacular talent, his sense of style and his youthful, handsome looks were the subject of music lovers and writers around the world, and attracted as well admirers of both sexes. Although he married in 1965, he reportedly maintained a long-lasting relationship with Gian Carlo Menotti.