Born in Belfast, she was educated at a Dominican convent and Queen's University, Belfast. She has worked as a teacher in her native Belfast at St. Patrick's College, Knock and an editor and is a former Writer in Residence at Queen's University, Belfast (1985–1988) and former visiting poet and instructor in creative writing at the University of California, Berkeley (1991).

Her first published poems appeared in two pamphlets, Single Ladies: Sixteen Poems and Portrait of Joanna, in 1980, the year in which she received an Eric Gregory Award. In 1981 she co-published Trio Poetry 2 with fellow poets Damian Gorman and Douglas Marshall, and in 1989 she collaborated with Nuala Archer on Two Women, Two Shores. Medbh McGuckian's first major collection, The Flower Master (1982), which explores post-natal breakdown, was awarded a Rooney prize for Irish Literature, an Ireland Arts Council Award (both 1982) and an Alice Hunt Bartlett Prize (1983). She is also the winner of the 1989 Cheltenham Prize for her collection On Ballycastle Beach.

Medbh McGuckian has also edited an anthology, The Big Striped Golfing Umbrella: Poems by Young People from Northern Ireland (1985) for the Arts Council of Northern Ireland, written a study of the car in the poetry of Seamus Heaney, entitled Horsepower Pass By! (1999), and has translated into English (with Eiléan Ní Chuilleanáin) The Water Horse (1999), a selection of poems in Irish by Nuala Ní Dhomhnaill. A volume of Selected Poems: 1978-1994 was published in 1997, and among her latest collections are The Book of the Angel (2004) The Currach Requires No Harbours (2007), and My Love Has Fared Inland (2008).

Recent criticism of McGuckian has pointed to her extensive use of unacknowledged source material, from Russian poetry and elsewhere, a discovery that may have motivated her decision to name (on the acknowledgements page) the primary source for her collection, The Currach Requires No Harbour.

She was awarded the 2002 Forward Poetry Prize (Best Single Poem) for her poem 'She is in the Past, She Has This Grace', and was shortlisted for The Irish Times Poetry Now Award for The Currach Requires No Harbour.

She is married to the poet John McGuckian.