Muñoz was the third overall pick in the 1980 NFL Draft by the Cincinnati Bengals. Muñoz's agent was Michael Trope, known as Mike during his days as an NFL agent. His selection was viewed as a major risk by many pundits since knee problems limited the 6 ft. 6 in., 280-pound Muñoz to just a combined eight games in his junior and senior seasons, though he did return for USC's 17-16 Rose Bowl win over The Ohio State University on New Year's Day 1980. However, Muñoz became a starter in his rookie season and remained a fixture at left tackle for the Bengals for 13 seasons and is considered one of, if not the greatest offensive linemen in NFL history. Despite his history of injuries, Muñoz missed just three games during his first 12 seasons. His rigorous workout routine included working out in the weight room he had installed in his home and running three to four miles every day.
In addition to his talents as a blocker, Anthony Muñoz was also a capable receiver, notching 7 receptions for 18 yards and scoring 4 touchdowns on tackle-eligible plays, including one in 1984 from left-handed rookie quarterback Boomer Esiason against their upstate rival, the Cleveland Browns in Cleveland.
In 1998, Anthony Muñoz was enshrined in the Pro Football Hall of Fame. He was the first Cincinnati Bengals player to be enshrined. Shortly after receiving the honor, Muñoz's hometown of Ontario, California renamed its Colony Park "Anthony Muñoz Hall of Fame Park". The renaming ceremony was held on June 26, 1998, and was attended by Muñoz, his family, city officials, and Ontario residents. The park, incidentally, is the place where Muñoz met his wife DeDe after a pickup softball game during his youth.
In 2002, the Anthony Muñoz Foundation was created to consolidate Muñoz's charitable activities and encourages area individuals and businesses to "...impact area youth mentally, physically and spiritually".