Calcavecchia was born in Laurel, Nebraska in 1960. While he was a teenager, his family moved from Nebraska to West Palm Beach, Florida. He attended North Shore High School in West Palm Beach and won the Florida high school golf championship in 1977. While playing in junior tournaments, he often competed against Jack Nicklaus' son, Jackie and as a result began a lifelong friendship at the age of 14 with the legendary pro.

Calcavecchia turned professional in 1981 and joined the PGA Tour in 1982. He was at his best in the late 1980s. His most notable achievement was in 1989, when he won The Open Championship (the British Open). Calcavecchia's only multiple-win season was in 1989 on the PGA Tour, with two other titles complementing the Open. He came closest to winning the Masters in 1988, finishing second by a single stroke and in 1992, he tied the record for the lowest score on the back nine in the Masters with a 29.