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.

• Our Only May Amelia (1999)
• The Creek (2003)
• Middle School Is Worse Than Meatloaf: A Year Told Through Stuff (2007)
• Penny from Heaven (2007)

Boston Jane novel series

• An Adventure (2001)
• Wilderness Days (2002)
• The Claim (2004)

Babymouse Series

• Queen of the World (2005)
• Our Hero (2005)
• Beach Babe (2006)
• Rock Star (2006)
• Heartbreaker (2006)
• Camp Babymouse (2007)
• Skater Girl (2007)
• Puppy Love (2007)
• Monster Mash (2008)
• The Musical (2009)
• Dragonslayer (2009)
• Burns Rubber (2010)
• Cupcake Tycoon(2010)

The Stink Files series

• The Postman Always Brings Mice (2004) (with Jonathan Hamel)
• To Scratch a Thief (2004) (with Jonathan Hamel)
• You Only Have Nine Lives (2005) (with Jonathan Hamel)