Kat Dennings was born and raised in the Bryn Mawr area near Philadelphia, Pennsylvania. Her mother, Ellen Judith Litwack, is a poet and speech therapist, and her father, Gerald J. Litwack, is a molecular pharmacologist and the chair of the Basic Sciences department of The Commonwealth Medical College in Scranton, Pennsylvania. Dennings is the youngest of five children, including an older brother, Geoffrey S. Litwack. Her family is Jewish.
Kat Dennings was home schooled; her only enrollment at a traditional school was for a half-day at Friends' Central School. She graduated from high school early, at the age of 14. She moved with her family to Los Angeles, California around 2002 so that she could act full time. She adopted the name Kat Dennings as her professional name when she was younger. According to Kat Dennings, as stated in Interview magazine in 2007, her parents initially considered her idea of pursuing an acting career to be "the worst idea ever".