The 1959–60 season marked the end of a business deal with the
San Francisco Giants that resulted in the participation of that team's prospects for Santurce, when
Ray Murray was fired from the manager office after shifting Cepeda to the left field and recording a losing record. Olmo became the team's new manager and the team recovered Pizarro in a trade with Caguas. The
Asociación de Jugadores de Puerto Rico (lit. "Puerto Rico Players Association") was formed, with Gómez and Santiago representing the Cangrejeros. Santurce advanced to the semifinals, where they defeated Caguas twice before losing the remaining three games. The Cangrejeros finished last during the first half of the 1960–61 season and were the runner-up of the second, but this result eliminated them under a short-lived league format where only the winners of one the halves advanced to the finals. During the 1961–62 season, the team shared its home stadium, Estadio Sixto Escobar, with the Senadores, eventually moving to
Hiram Bithorn Stadium. The Cangrejeros advanced to the playoffs, defeating Caguas in a seven-game semifinal. Santurce won the finals series sweeping the Indios. Cepeda broke a record by hitting 19 home runs throughout the season, while Pizarro did so by recording seven straight strikeouts against Ponce as part of his fifth consecutive year leading the LBPPR in strikeouts. The team went on to become the only LBPPR team to win the
Interamerican Series, which were held in their home field. In the 1962–63 season, the Cangrejeros lost Cepeda, but reinforced its roster with prospects from the
Cleveland Indians. The team advanced to the playoffs, but lost its semifinal to the Criollos. However, Pizarro was signed as the Indios' reinforcement for the Interamerican Series, pitching the only no-hitter in the event's history, which included ten strikeouts. Santurce's José Géigel was the LBPPR's Rookie of the Year. Cepeda returned to play during the 1963–64 season and was joined by
José Tartabull. The Cangrejeros finished in the fourth place of the pennant race, but won the "City Championship". Santurce won the pennant and advanced to the playoffs, where they defeated San Juan in the semifinals and went on to win the final series against the Indios. On January 9, 1965, the team was involved in an uncommon historic event, when Mayagüez's first baseman, Fred Hopke, did not receive the ball once, going throughout the game without recording an assist or out at first base. Staehle was the league's MVP, while Pizarro was the team's dominant pitcher. Olmo returned to the manager office in 1965–66, but the team struggled during the initial half, losing ten straight games to open the season, being unable to recover, finishing last in the standing. This was Olmo's final participation with the Cangrejeros. In the 1966–67 season, the team developed a working agreement with the
Baltimore Orioles, which was product of
Earl Weaver being signed to serve as manager. Santurce finished second in the regular season, losing a tie-breaker for the first place. In the semifinals, they defeated Arecibo in straight games to advance. The Cangrejeros won the championship against regular-reason champion, Leones de Ponce. The pitching staff, which included Pizzaro and Gómez, was responsible for this success, averaging a combined 1.93 ERA during the first two halves. In the 1968–69 season, the Cangrejeros were managed by
Frank Robinson. The team won the regular season title by earning their best record up to that year, but lost their semifinal series against the Senadores. Its pitcher,
Jim Palmer, threw the first no-hitter in franchise history. In 1969–70, the team advanced to the semifinals, where the defeated the Indios following a solid performance by
Fred Beene. However, for the third straight year, the team failed to win a series championship against Ponce. Despite this, the race for the "City Championship" was intense, being highlighted by a no-hitter and a fan incident involving Miguel Cuéllar. Pérez went on to reinforce Ponce in the Caribbean Series, the first held in a decade. In 1970–71, the Cangrejeros signed
Reggie Jackson. The team advanced to the playoffs, winning their semifinal against the Senadores. In the finals series, Santurce defeated Caguas to win its eight championship. The team's performance in the series was not enough to compete for the title. Gómez served as the Cangrejeros' manager during the following season. The team advanced to the playoffs, finishing third during the regular season. However, despite having Cepeda and the league's batting champion,
Don Baylor, they failed to win their semifinal against the Leones. The team's pitcher,
Roger Moret, was the league's best starter that year, with a record of 14–1. Robinson returned to the manager office in 1972–73. Pizarro and Moret were joined by several prospects from the
Los Angeles Dodgers in the lineup. Santurced finished first in a regular season that was interrupted by Clemente's death in an airplane accident. The team finished second in the Caribbean Series. In 1973–74, Santurce signed
Gil Flores, who served as a reserve player. The Cangrejeros maintained the fourth place of the standings throughout the season, while experiencing defensive lapses in its infield defense. Arturo Miranda,
Luis Alcaraz and Manuel Ruiz were employed to compensate in the infield. However, the team was eliminated during the regular season in a sudden death game against Arecibo. Two different managers would fill the role for the next three years. The league reduced the season to sixty games in 1975–76. Moret and
Gilberto Rondón served as the team's main players, while Gómez and Pizarro played another year.
Juan Beníquez and
Sandy Alomar Sr. complimented them. Santurce was able to clinch the final playoff berth, defeating the Leones in a series. The Cangrejeros advanced to the semifinals, losing a seven-game series against the Criollos. Pizarro played his final season with the team in 1976–77, while Gómez was signed to the Vaqueros. He, Moret, Rondón,
Ramón Hernández and Esteban Texidor were the team's main figures. The Cangrejeros finished in the fourth place of the regular season standing. Despite having a lineup that included Alomar, Ismael Oquendo, Ruiz, Beníquez and
Puchy Delgado among others, Santurce failed to qualify to the post-season in 1977–78. This was
Elrod Hendricks final season with the Cangrejeros. Hiram Cuevas, who was the team's general manager, ran the team on a trust established by Poto Paniagua years before. ==1980–2000: Influx of MLB players==