Holm was raised in Audubon, Pennsylvania with her four brothers. After graduating from Dickinson College in Carlisle, Pennsylvania, she worked in television and later began to write. Our Only May Amelia, the story of a 12-year-old girl living in the late 1800s, inspired by a diary written by her great aunt, became her first published novel and was a 2000 Newbery Honor Book. Holm also has written a series starring Jane Peck, a young woman living in the 1850s (Boston Jane: An Adventure, Boston Jane: Wilderness Days and Boston Jane: The Claim); The Creek, a horror thriller; a series of graphic novels for young adults illustrated by her brother Matthew (Babymouse: Queen of the World, Babymouse: Our Hero, Babymouse: Beach Babe, Babymouse: Rock Star, Babymouse: Heartbreaker, and Camp Babymouse); and The Stink Files, a series co-written with her husband Jonathan Hamel starring James Edward Bristlefur, a cat raised by a British secret agent who is adopted by an American family and renamed Mr. Stink after his owner is murdered. Penny from Heaven, a story set in the 1950s starring an 11-year-old Italian-American girl, was a 2007 Newbery Honor recipient.
Our Only May Amelia has been adapted for the stage by John Olive. The River Theater in Astoria, Oregon performed it for its 2006 summer run, in conjunction with FinnFest USA '06. The events of the play (and book) were set just north of Astoria in Naselle, Washington.