Manzanillo played with the Chicago White Sox and Pittsburgh Pirates over parts of three seasons spanning 1988–1994. Listed at 6' 1" (1.83 m), 210 lb. (95 k), he batted and threw left-handed.

Manzanillo posted a 4–3 record with a 4.43 earned run average in 53 games for the White Sox and Pirates. He also spent 18 seasons in the Minor Leagues from 1981–2005, including stints in the Korea, Taiwan and Mexico baseball circuits.

In between, Manzanillo played winter ball with the Leones del Caracas club of the Venezuelan League, and for the Tigres de Licey and Leones del Escogido of the Dominican League. In addition, he served as a reinforcement for the Águilas Cibaeñas in the 1986 Caribbean Series.

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