He began his baseball career in 1955 in Puerto Rico as a pitcher for the Cangrejeros de Santurce.

After going 27–6 with a 2.06 earned run average in the minors,[2] he made his major league debut on May 4, 1957, against the Pittsburgh Pirates at 20 years of age.

He pitched seven strong innings, giving up only one run, however, the Braves managed only two hits off opposing pitcher Vern Law, and Pizarro lost his debut, 1–0.

The Braves beat the New York Yankees in a seven-game World Series that year; Pizarro's only appearance came in Milwaukee's 12–3 loss in game three.

In 1961, despite being the youngest pitcher in the starting rotation, Pizarro emerged as the staff's ace, leading the Chisox with fourteen wins, 188 strikeouts and 194.2 innings pitched.

[10] Though he made nine starts for the 1967 Pirates, he was mainly a relief pitcher, earning a career high nine saves.

He was traded along with Ken Harrelson and Dick Ellsworth from the Red Sox to the Cleveland Indians for Sonny Siebert, Vicente Romo and Joe Azcue on April 19, 1969.

After beginning the 1970 season with Oakland's triple A affiliate, Pizarro was released and signed a minor league contract with the California Angels.

He was 9–0 for the Hawaii Islanders when the Angels dealt him to the Chicago Cubs for Archie Reynolds.

[13] In his next start, he shutout Tom Seaver and the New York Mets 1–0 at Shea Stadium.

He spent most of the first half of the 1973 season assigned to the Cubs' triple A affiliate, the Wichita Aeros.

The Pirates won the National League East by a game and a half over the St. Louis Cardinals, allowing Pizarro to return to the post season for the first time since 1958.

His regular-season count is 392: 197 in the US (131 in the majors and 66 in the minors), plus 38 more in Mexico in his late 30s and 157 while playing winter ball in his homeland.