Shalhoub, the ninth of ten children, was born and raised in a Maronite Christian family in Green Bay, Wisconsin. His father, Joe, was from Lebanon and emigrated to the United States as an orphan at the age of eight. He was a meat peddler who drove a refrigerated truck. Joe married Shalhoub's mother, Helen (née Seroogy), a second-generation Lebanese-American. Shalhoub was introduced to acting by an older sister who put his name forward to be an extra in a high school production of The King and I. Despite finding himself standing on the wrong side of the curtain during the final dress rehearsal, he became enamored of the theater. Shalhoub attended Green Bay East High School. There is a widespread belief that in his senior year he suffered a setback by breaking his leg in a fall off the stage into the pit during a rehearsal, but in a keynote talk for a film festival at the University at Albany in Albany, New York in November 2019, Shalhoub corrected this and said it “never actually happened. ” He performed in the school's final play that year.