Karen Hesse was born in Baltimore, Maryland. She studied math at nearby Towson State College and married Randy Hesse in 1978 before completing her studies. She attended college at Towson University, the University of Maryland and College Park. She earned a B.A. in English with double minors in psychology, and anthropology, during which she began writing poetry.

Her first novel was a rejected story about meeting Bigfoot, but her next proposal was published by Henry Holt in 1991 as Wish on a Unicorn.

Stowaway, first published in 2000 by Simon & Schuster USA, is based on the true story of an 11-year-old boy who stowed away on Captain James Cook’s ship Endeavour in 1768. The UK version of this book is published under the title Young Nick’s Head. It is in the format of a diary written by Nicholas Young, the cabin boy on the Endeavour.

Hesse tackled a more disturbing subject in the 2001 verse novel Witness. The Ku Klux Klan, re-invigorated in the 1920s (in this book, 1924 and ’25) tries to take over a small Vermont town. The book is written from the perspectives of several people – Merlin Van Tornhout and Johnny Reeves, both members of the Klan; Sara Chickering, a farmer; Esther Hirsh, a six-year-old Jewish girl; Leonora Sutter, an African American girl; Iris Weaver, a restaurateur; Harvey and Viola Pettibone, shop owners; Reynard Alexander, a newspaper editor; Fitzgerald Flitt, the doctor; and Percelle Johnson, the town constable. In Witness Hesse continued the distinctive poetic/prose style she pioneered in Out of the Dust.

In 2012 Hesse received the Phoenix Award from the Children’s Literature Association for Letters from Rifka, recognizing the best children’s book published twenty years earlier that did not win a major award.