Vacchiano was born in Portland, Maine, and took up the trumpet at age 12. Two years later, he joined the Portland Symphony, and also played with the 242nd Coast Artillery Band. He studied at Juilliard, then called the Institute of Musical Art, from 1931 to 1935.

In 1935, he joined the New York Philharmonic, having turned down a simultaneous job offer from the Metropolitan Opera; he was made principal trumpeter seven years later. During his 38 years with the orchestra, he performed and recorded with conductors Leonard Bernstein, Leopold Stokowski, Igor Stravinsky, George Szell, and Bruno Walter, among others.

Vacchiano was one of the first important American trumpet players to use an instrument tuned to the key of C (the standard trumpet is in B-flat), and according to Juilliard he helped to spread the practice of using instruments transposed to fit various works of music.

He also wrote a series of textbooks and designed a line of trumpet mouthpieces.

Vacchiano was a member of Juilliard's faculty from 1935 to 1998 and an emeritus professor from 1998 to 2002. He taught about 2,000 students, according to his own estimate; they included Wynton Marsalis, Miles Davis, Gerard Schwarz, and Philip Smith, the Philharmonic's current principal trumpeter.

In a statement, a spokesperson for the Philharmonic said, "William Vacchiano was a highly respected and beloved member of the New York Philharmonic over the course of several decades. His presence is still felt here, and will live on in the memory of the musicians, board and staff."

Juilliard president Joseph W. Polisi and chairman Bruce Kovner said, "The entire Juilliard community mourns the passing of William Vacchiano, one of the longest-serving faculty members in the history of the school. A person of impeccable musical integrity and great humanity, he was revered and loved by his students and friends. He will be deeply missed."