Mottram was born in London and educated at Purley Grammar School, Croydon, and Blackpool Grammar School, Lancashire. In 1943, he was awarded a scholarship to Pembroke College, Cambridge but opted to serve in the Royal Navy instead, only taking up the scholarship in 1947. He graduated with honours in 1950. Over the following decade, Mottram travelled extensively and worked as a teacher in Switzerland, Singapore and the Netherlands.

In 1960, Mottram returned to London and took a post as Lecturer in English and American Literature at King's College London. At the time, King's was one of very few British universities to offer American studies, and Mottram was to prove a pioneer in the field. He co-founded the Institute of United States Studies in 1963, the same year in which his tenure as a lecturer at King's was confirmed. In 1973, became Reader in English and American Literature and was appointed professor in 1982. In September 1990 he retired with the title Emeritus Professor of English and American Literature.

In the early sixties, Mottram travelled to the United States and met a number of writers, including William Carlos Williams, Allen Ginsberg and others. He became friendly with William Burroughs during his time in London. These contacts resulted in three of Mottram's best-known critical books; William Burroughs: the algebra of need (1971, British edition 1977), Allen Ginsberg in the Sixties (1972) and Paul Bowles: staticity & terror (1976). These studies did much to help introduce the Beat writers to a wider British audience.

Mottram's first book of poetry, Inside the whale was published by Bob Cobbing's Writers Forum in 1970. He went on to publish at least another 34 collections, including A Book of Herne: 1975-1981, Elegies (both (1981)) and Selected poems (1989).

His work clearly shows the influence of the American avant-garde poets he admired, particularly in his use of techniques such as found poetry, cut-up technique and collage, but it also has a distinctly British quality in the tradition of Basil Bunting.

An interview with Mottram appeared in the London based magazine Angel Exhaust, along with his poetry.

An interview and poetry reading, recorded in 1982, appears in My KPFA.

In 1971, Mottram was made editor of the Poetry Society's magazine Poetry Review. Over the next six years, he edited twenty issues that featured most, if not all, of the key poets associated with the British Poetry Revival and carried reviews of books and magazines from the wide range of small presses that had sprung up to publish them. Mottram also included work by a number of American poets, a fact that ultimately led to his removal from the post.

During this period, Mottram was twice a guest lecturer at Kent State University, where, along with Black Mountain poet Ed Dorn, he was an early supporter of the musical group Devo, and its founders Gerald Casale and Bob Lewis, whose poetry Mottram published when he was editor of the Poetry Review. He also edited The Rexroth Reader (1972) and the section of the 1988 anthology The New British Poetry that was given over to the poets associated with the Revival.