A two-sport star, Cisco earned All-American and All-Big Ten honors and was a captain on the 1957 Ohio State Buckeyes football team, which won the national championship with a 9–1 record, playing both fullback and linebacker.

A curveball specialist, Cisco entered the Majors in 1961 with the Boston Red Sox, playing a little over a season for them before the New York Mets acquired him via waivers on September 6, 1962.

He returned to the Red Sox for part of the 1967 season, then was acquired by the expansion Kansas City Royals, where he finished his active MLB career in 1969.

Following his playing retirement, Cisco became a pitching coach for the Royals, Montreal Expos, San Diego Padres, Toronto Blue Jays and Philadelphia Phillies, serving for all or parts of 28 years.

He spent six seasons with the Blue Jays (1990–1995), helping his team to win three consecutive American League East Division titles (1991–93) and two World Series (1992–93).