Maguire, born and raised in Albany, New York, is the middle child of seven. Schooled in Catholic institutions through high school, he received a BA in English and Art from the State University of New York at Albany, an MA in Children's Literature from Simmons College, and a PhD in English and American Literature from Tufts University. His doctoral thesis was about English-language fantasy written for children between 1938 and 1988. He was a professor and co-director at the Simmons College Center for the Study of Children's Literature from 1979 to 1986. In 1987, Maguire co-founded a nonprofit educational charity, Children's Literature New England, Inc., and was co-director for twenty-five years. He has been a board member of the National Children's Book and Literacy Alliance, and has served on boards at the Isabella Stewart Gardner Museum, the Board of Associates of the Boston Public Library, the Concord Free Press, among others.
Maguire has lived in Dublin, London, and the greater Boston area. While he published his first novel for children at the age of 24, his professional life includes commitments to literacy and literature education alongside his creative work. He met the American painter Andy Newman in 1997, and in 1999 they adopted the first of their three children. Two others followed in 2001 and 2002. Maguire and Newman were married in June 2004, shortly after gay marriage became legal in Massachusetts.
The novelist is an occasional reviewer for the Sunday New York Times Book Review. He has contributed and performed original material for NPR's "All Things Considered" and has lectured widely around the world on literature and culture. Maguire and his family were featured on "Oprah" and he was the subject of a Sunday New York Times Magazine profile by Alex Witchel. His adult novels regularly make New York Times and national bestseller lists. Egg & Spoon (2014), a fantasy for young adults, was a Boston Globe-Horn Book Honor Book and is under option by Universal Studios; After Alice (2015), a novel for adults, is published on the occasion of the 150th anniversary of Alice's Adventures in Wonderland. As of 2015, Maguire is a Roman Catholic.