He is the son of Lewis Stine, a shipping clerk, and Anne Feinstein. His family was Jewish. He began writing at age nine, when he found a typewriter in his attic, subsequently beginning to type stories and joke books. He graduated from Ohio State University in 1965 with a Bachelor of Arts in English. While at OSU, R. L. Stine edited the OSU humor magazine The Sundial for three out of his four years there. He later moved to New York City to pursue his career as a writer.
Stine created the humor magazine Bananas. In 1986, Stine wrote his first horror novel, called Blind Date. He followed with many other novels, including The Babysitter, Beach House, Hit and Run, and The Girlfriend. He was also the co-creator and head writer for the Nickelodeon children's television series Eureeka's Castle.