Giambrone was born in St. Joseph, Michigan. His family is of Italian and German descent. The family moved from Michigan to Park Ridge, Illinois when he was a young child.
He attended Lincoln Middle School, and Maine South High School. He now splits his time between Los Angeles and Park Ridge.
Sean took up acting at the age of 9, starring in television commercials for McDonald's and Friendly's Restaurants among others.
In 2014, Giambrone joined the voice cast of the animated series Clarence, which aired on Cartoon Network, providing the voice of Jeff, a friend of the title character. He also made an appearance in R.L. Stine's The Haunting Hour, and provided the voice of a bull terrier named Russell in the DVD film Russell Madness.