Meloni was born in واشینقتن، دی.سی., the youngest of three children (he has a brother and sister) of Cecile (née Chagnon; 1926–2016), a homemaker, and Charles Robert Meloni (1927–2012), an endocrinologist. His maternal ancestry is French Canadian and his paternal ancestry is Sardinian (from ایتالیا). Meloni attended St. Stephen's School (now St. Stephen's & St. Agnes School) in Alexandria, Virginia, and played quarterback on the football team. He studied acting at the University of Colorado at Boulder and graduated with a degree in history in 1983. After graduation, Meloni went to New York where he continued his studies with Sanford Meisner at the Neighborhood Playhouse, as well as the Center for the Media Arts.