He was selected in the first round of the 1981 NFL draft, and played professionally for the Washington Redskins, San Diego Chargers, and Arizona Cardinals.

As a senior in 1980, he was a unanimous first-team All-American and received the Outland Trophy as the nation's top collegiate interior lineman.

As a part of the 1980 Pittsburgh Panthers football team, he played with future NFL players Dan Marino, Dwight Collins, Rickey Jackson, Russ Grimm, Jimbo Covert, Bill Maas, Hugh Green, and Tim Lewis.

Under the tutelage of head coach Jackie Sherrill, May and his teammates led Pitt to a 39–8–1 four-year record, which included three top-10 finishes and four bowl games.

He was inducted into the College Football Hall of Fame in 2005, becoming the 23rd Pitt player or coach to earn the honor.

He signed with the San Diego Chargers, playing as Dave Richards' backup during the 1991 season.

[10] He later played for the Phoenix Cardinals (1992–93), where he reunited with Joe Bugel, the Redskins' offensive line coach from 1981 to 1989, before his retirement in 1993.

[14] After TNT lost the broadcasting rights to Sunday Night Football following the 1997 season, May joined CBS Sports in 1998 as a game analyst for its NFL coverage from 1998 to 2001.

[13] He also spent the 2000 season calling Arena Football League games on the original TNN Cable Network alongside Eli Gold and Jill Arrington, which culminated with the inaugural af2 Arena Cup in 2000 between the Tennessee Valley Vipers and the Quad City Steamwheelers.