He played in Major League Baseball (MLB) for the Philadelphia Phillies (1963–1966), Chicago Cubs (1967), and Boston Red Sox (1968–1973).

As a junior pitcher in 1958, Culp won six postseason games, including a no-hitter, in leading the team to the state title.

[3] At 17, Culp was offered contracts with 15 of the 16 major league baseball teams, signing as an undrafted free agent with the Philadelphia Phillies for $100,000.

In 1962, he played for the Williamsport Grays of the Eastern League, with a 3.20 earned run average (ERA), and a 13-8 win-loss record.

[6] As a rookie, he made the 1963 NL All-Star squad[7] and went on to retire Al Kaline, Frank Malzone, and Carl Yastrzemski (around a Leon Wagner single),[citation needed] in a scoreless fifth inning[8] of the Senior Circuit's 5–3 victory.

[5] Culp returned to the All-Star game in 1969,[14] pitching a perfect ninth inning for the American League (AL).

He retired Pete Rose (on a foul pop fly) and struck out Randy Hundley and Tony Pérez.