Fain was born in San Antonio, Texas. The lefty was a top prospect and had 461 at bats in his rookie season, playing full-time. That year, he batted a solid .291 with 7 home runs and 71 RBIs.

Not until 1951 would Fain have a much better season. In '51, he batted .344 with 6 homers and 57 RBIs, only picking up 425 at bats on the season due to a broken foot. Even so, his pure hitting numbers were incredible. That year, and the following, he finished 6th in Most Valuable Player Award voting. Yogi Berra won in '51 and teammate Bobby Shantz took the prize in '52. Although, in both years, Fain took home batting titles.

Fain was sometimes considered the best fielding 1B in the majors until Vic Power showed up.

He had an off-year in 1953, after getting into a brawl in a Maryland café with White Sox fans. Fain was fined by the White Sox for 600 dollars. He was then sued for 50,000 dollars. After a knee injury the following year, he never really got back on track. He ended having had an on-base percentage over .400 every full year that he played. He was in the top 10 in that category, seven times in his career, while being in the top 10 in base on balls eight times in his career. His ability to get on base helped him to 5 straight All-Star Games (1950-1954).

In a 9-season career, he batted .290 with 48 home runs and 570 RBIs. He had 213 career doubles and a career .424 on-base percentage. He had 1139 career hits in 3930 at bats, and 1151 games.

He died in Georgetown, California of leukemia along with other complications. He was 80 years old.