In 1959, his second season in the Baltimore farm system, Nicholson batted .298 for their Aberdeen Pheasants affiliate (managed by Earl Weaver) with 35 home runs, tied for the lead in the Class C Northern League.

Strikeouts would prove to be Nicholson's Achilles heel during his big-league career; in 1964, his second consecutive season as the White Sox' regular left-fielder, he fanned 126 times, fifth in the American League.

On May 6, 1964, during the first game of a doubleheader at Comiskey Park, Nicholson hit a home run off Moe Drabowsky of the Kansas City Athletics that either bounced off the left-field roof or entirely cleared it.

After the 1965 campaign, the White Sox traded Nicholson and catcher Bill Heath to the Houston Astros for pitcher Jack Lamabe and cash.

[5] The Astros traded Nicholson and Bob Bruce to the Atlanta Braves for Eddie Mathews, Arnold Umbach, and a player to be named later after the 1966 season.