Born in Leamington, Warwickshire, Mellers was educated at the local Leamington College and later won a scholarship to Downing College, Cambridge, where he read English under F. R. Leavis. He later lodged with the Leavises for three years while pursuing a Music degree.
After writing many articles for Leavis's journal Scrutiny since the September 1936 issue, he appeared on the editorial board of the January 1942 issue, and continued in that position until the December 1948 issue.
In 1945 Mellers was appointed to teach English and music at Downing College, and in in 1949, he became extra-mural tutor in music at Birmingham University. In 1960-62 he was Andrew Mellon visiting professor of music at the University of Pittsburgh. From 1964 until 1981 he was founding professor and head of the Music Department at the University of York; he remained emeritus professor of music there until his death. He was also an honorary fellow at Downing College, Cambridge. On 12 July 1981, he received an honorary degree of music from the City University, London.
The 2004 York Late Music Festival opened with a weekend tribute to Mellers. A 90th-birthday tribute concert was held in October 2004 at Downing College, featuring music by Mellers as well as new pieces written for the occasion by Stephen Dodgson, David Matthews and Howard Skempton, among others.
- Music and Society: England and the European Tradition (1946)
- Studies in Contemporary Music (1947)
- Francois Couperin & the French Classical Tradition (1950)
- Music in the Making (1951)
- Romanticism and the 20th Century, from 1800 (1957)
- The Sonata Principle, from c. 1750 (1957)
- Man and His Music (1962; Vols. 3 & 4 by Mellers)
- Music in a New Found Land: Themes and Developments in the History of American Music (1964)
- Harmonious Meeting: A study of the relationship between English music, poetry and theatre, c.1600 (1965)
- Caliban Reborn: Renewal in Twentieth-Century Music (1968)
- Twilight of the Gods: the Beatles in Retrospect (1973)
- Bach and the Dance of God (1980)
- Beethoven and the Voice of God (1983)
- A Darker Shade of Pale: a Backdrop to Bob Dylan (1984)
- Angels of the Night: Popular Female Singers of Our Time (1986)
- Le Jardin Retrouve. The Music of Frederick Mompou 1893-1987 (1987)
- The Masks of Orpheus: Seven Stages in the Story of European Music (1987)
- Vaughan Williams and the Vision of Albion (1989)
- Percy Grainger (1992)
- Francis Poulenc (1993)
- Between Old Worlds and New (1997)
- Singing in the Wilderness: Music and Ecology in the Twentieth Century (2001)
- Celestial Music?: Some Masterpieces of European Religious Music (2002)
- Boris Ford, Obituary, Wilfrid Mellers, The Guardian, 19 May 2008.
- Gordon Rumson (April 2004). "Scrutiny: Wilfrid Mellers' early writings".