Gain played tackle, middle guard, and end and was standout defender at tackle, end, and middle guard. Cleveland led the NFL in many defensive categories in his 12 years and the Browns won two thirds of their games and three championships during his career.
Gain was a standout offensive and defensive lineman at the University of Kentucky, where he won the Outland Trophy in 1950 as the nation's Outstanding College Interior Football Lineman of the Year. Gain started at tackle four years (1947–1950) at the University of Kentucky (SEC). At Kentucky he won All-American honors his last two years (consensus in 1950) and co-captained a Wildcats team that captured the SEC championship. In 1950, the three-year All-SEC selection was chosen the best SEC lineman by the Atlanta (GA) Touchdown and Birmingham (AL) Quarterback Clubs. He was inducted into the College Football Hall of Fame in 1980.
After playing one season in Canada in 1951 with the Ottawa Rough Riders of the Canadian Football League, he returned to Cleveland and played for twelve years (1952, 1954–1964). Gain played defensive tackle for the Cleveland Browns (NFL). A stalwart defensive tackle on six Browns Eastern Conference and three (1954–1955, 1964) NFL championship teams, Gain started in five Pro Bowl games.
He was honored by the Pittsburgh (PA) Dapper Dan Club and was named to the West Virginia and Cleveland Sports Hall of Fame.
He ended his career with a one-time All-Pro and a 7-time Second-Team All-Pro record in his 12 seasons, and after the 1957 season was voted the NFL Defensive linemen of the year by the Los Angeles Times.
He ended his career with three NFL championships with the Browns.