Margaret Avison was born in Galt, Ontario in 1918. She moved to Regina with her family in 1920, and then to Calgary a few years later. The Avisons moved to Toronto in 1930, where Avison attended high school. She entered Victoria College at the University of Toronto in 1936. When she completed her B.A. in English in 1940, she was already a published poet; her poem "Gatineau" had appeared in the Canadian Poetry Magazine the previous year. Avison had a wide and varied professional career including working as a file clerk, proofreader, editor, and in the Registrar's Office and Library at the University of Toronto.

In 1951, Avison's History of Ontario, a high school textbook, was published. She was awarded a Guggenheim Memorial Foundation Grant in 1956, enabling her to spend eight months in the United States writing poetry and attending creative writing classes at the universities of Chicago and Indiana. She then undertook freelance work editing, indexing, and ghostwriting a book entitled A Doctor's Memoir. Her first book of poetry, Winter Sun, was published in 1960 and won the Governor General's Award.

Deeply moved by the Hungarian Uprising of 1956, Avison translated eight Hungarian poems, which appeared in The Plough and Pen: Writings from Hungary 1930-1956, which brought recognition to many of the great twentieth-century Hungarian poets. The following year The Research Compendium was published. In 1963 Avison returned to the University of Toronto for graduate work. She completed her M.A. thesis and began doctoral studies in 1964, but never earned her doctorate because she did not write a thesis.

The Dumbfounding, her second book of poetry was published in 1966. From 1966-1968 she taught at Scarborough College, University of Toronto. During this time, she volunteered as a women's worker for a Presbyterian mission called Evangel Hall. In 1973 Avison spent eight months as writer-in-residence at the University of Western Ontario, after which she took a position in the CBC Radio Archives. In 1978 she returned to charitable work, working as a secretary for the Mustard Seed Mission. In 1978 her third book of poetry, sunblue, was published. It was the product of her profound religious convictions.

In 1986 Avison retired from the Mustard Seed Mission. She received her second Governor-General's Award in 1990 for No Time, which had been published the previous year. An anthology of her work titled Margaret Avison: Selected Poems was published in 1991. In 1994, A Kind of Perserverance was published, consisting of two lectures describing the tensions she experienced when trying to live out her Christian values in secular society, specifically within a university setting. A further book of poetry, Not Yet but Still, was published in 1997. Her book of poetry Concrete and Wild Carrot, which was published in 2002 by Brick Books, won the prestigious Griffin Poetry Prize in 2003. Between 2003 and 2005 the Porcupine's Quill published Always Now: The Collected Poems, Volumes One to Three. In her later years, Avison published three books, two of them post-humously: Momentary Dark (2006), Listening (2009), and I Am Here and Not Not-There, an autobiography (2009). In addition to her two Governor-General's awards, Avison's contribution to Canadian literature has been recognized through the bestowal of honorary degrees from Acadia University (1983), York University (1985), and Victoria University (1988). Avison was made an Officer of the Order of Canada in 1985. She died in 2007.