Skyler Gisondo grew up in California. He was home schooled for several years to give him free time for acting; then he attended Milken Community School, a Jewish high school, graduating in 2014. He was deeply involved in Jewish activities, including Temple Beth Am (Conservative Judaism), USY (United Synagogue Youth) and Camp Alonim. In 2015 he began attending the University of Southern California, a semester at a time to make room for Santa Clarita Diet.
In high school and college, Skyler found some hunky friends who enjoyed homoerotic horseplay. Some have remained part of his crew to this day.