His first book was a poem, Malady, published in 1970. It consisted of just four words ("malady", "melody" and "my lady") arranged in patterns on the page, accompanied by drawings by artist Ralph Hotere, who had met Manhire in Dunedin while he was the Frances Hodgkins Fellow. Manhire's second book, The Elaboration (1972), was also a collaboration with Hotere, and was published by Charles Brasch and Janet Paul. Around this time, and while living in London, Manhire and fellow poet Kevin Cunningham set up the Amphedesma Press to publish their own and their friends' work, including poetry books by Ian Wedde and Bob Orr. In 1973, after returning to New Zealand, Manhire began lecturing in the English department of Victoria University of Wellington, where he founded New Zealand's first creative writing course in 1975. His creative writing course, which he taught for more than 25 years, had a major influence on New Zealand literature, with many well-known New Zealand writers having graduated, including Elizabeth Knox, Barbara Anderson and Jenny Bornholdt. Mutes & Earthquakes (1997) was an anthology of works by his former students; the introduction by Manhire begins with two pieces of advice: "1. Write what you know, and / 2. Write what you don't know". From 2001 to 2013 he was the inaugural and founding director of the International Institute of Modern Letters, which offers an MA and Ph.D. in creative writing, as well as a range of specialised undergraduate workshops. Students of the Institute have included Eleanor Catton, Catherine Chidgey and Hinemoana Baker. In 2016 the institute's building was named the Bill Manhire House in recognition of his contribution to the university and to New Zealand literature. His successor Damien Wilkins said on the occasion that Manhire's name "is synonymous with creative writing at Victoria". Manhire has published a number of poetry collections, including notably his Collected Poems (2001). His poetry is known for word-play, experimentation and his ironic and whimsical sense of humour. Critic Iain Sharp writes that Manhire's reputation "rests on a solid, seriously intentioned body of work, notable for its oblique lyricism and sense of wonder at the strangeness of both life and language". After his fifth book of poetry, Good Looks (1982), Manhire for a time switched to writing prose, publishing The Brain of Katherine Mansfield (1988), a book in the style of the Choose Your Own Adventure series with illustrations by Gregory O'Brien,