Grealy was born in Dublin, Ireland, and her family moved to the United States in April 1967, settling in Spring Valley, New York. She was diagnosed at the age of 9 with a rare form of cancer called Ewing's sarcoma. Treatment for this often fatal cancer (Grealy reports an estimated 5% survival rate) led to the removal of her jawbone, and over the following years she had many facial reconstructive surgeries. The book describes how she weathered the cruelty of schoolmates and others, suffering taunts and endless stares from strangers.

At 18, Grealy entered Sarah Lawrence College where she made her first real friends and nurtured her love of poetry. She graduated in 1985 and went on to study at the Iowa Writers' Workshop. In Iowa she lived with fellow writer Ann Patchett. Their friendship is the subject of Patchett's 2004 memoir A Friendship.

She also published a collection of essays in 2000, titled As Seen on TV: Provocations.

Following her final reconstructive surgery, Grealy became dependent upon her prescribed painkiller, OxyContin, as she had earlier with codeine. She died of an accidental drug overdose on December 18, 2002, in New York City, at the age of 39.

Her sister, Suellen Grealy, is opposed to Ann Patchett's depiction of Lucy in Truth & Beauty. She claims that Patchett and the book's publisher Harper Collins stole the Grealy family's right to grieve privately.

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