Pérez played his first major league game on July 27, 1993, as the host Angels defeated the Oakland A's 15–8. Starting at third base and batting sixth, he had three at-bats, two hits, a walk, three runs batted in and three runs scored. His first at-bat resulted in a first-inning walk against Bobby Witt.
Perez recalled that first at-bat as an announcer on the May 6. 2019, ESPN Monday Night Baseball broadcast. Perez had swung at a slider that was over a foot and a half off the plate to honor a childhood pact with his brother that if either of them made it to the major leagues they agreed to swing at the first pitch.
An inning later he got his first career hit, a double off reliever Joe Boever. In the eighth inning, Pérez hit his first home run, a 3-run shot off Kevin Campbell, scoring teammates Tim Salmon and Chili Davis.[8]
He also hit the first of his three career walk-off home runs in 1993.[9] The Angels trailed the Minnesota Twins 3–2 in the bottom of the ninth inning with Salmon on base and one out. Pérez homered to left field off Twins reliever Rick Aguilera for a 4-3 Angels win.[10]
Pérez's most productive year came in 1997 for the Cincinnati Reds. In 330 plate appearances, he hit .253 with 16 home runs, 52 runs batted in, 18 doubles, 29 walks and five stolen bases. In 2003 for the St. Louis Cardinals, in 289 plate appearances, he hit .285 with 11 home runs, 41 runs batted in, 16 doubles, 29 walks and five stolen bases.[11]
One pitcher that Pérez had the most success against was one of the all-time dominant hurlers, Hall of Famer Randy Johnson. On April 19, 2005, starting at first base for Tampa Bay against the New York Yankees in Yankee Stadium, Pérez hit two home runs (in consecutive at-bats) and knocked in three runs against Johnson.[12] through that game. Perez was 8-for-27 lifetime against Johnson, with four home runs, seven runs batted in and two doubles.[13] In 2006, Pérez's last season, Johnson was ejected and suspended five games for a brushback pitch against Pérez a half-inning after Johnson's teammate, Jorge Posada, had been hit by a pitch.[14]
Pérez's four home runs against Johnson were the most against one pitcher in Pérez's career. He hit three each off Al Leiter and Sterling Hitchcock.[9]
Pérez also was known for some big pinch-hit home runs during his career, including three in one season (2002) for the Cardinals and seven for his career.[15] His game-winning pinch-hit home runs included an 11th-inning shot for the Reds off Los Angeles Dodgers pitcher Mark Guthrie in 1997,[16] an eighth-inning two-run shot for the Cardinals off New York Mets pitcher Al Leiter in 2002, and a ninth-inning walk-off solo shot for the Devil Rays against pitcher Alan Embree.[17][18]
In late 2007, three months after the Puerto Rican winter baseball league was cancelled after 69 seasons, Pérez returned to Puerto Rico and announced his founding of the Winter Training Program (WTP) for both professional and amateur players in an effort to return pro baseball back to the island. The program was sponsored by the government municipality of San Juan, Major League Baseball, and private donors.[22]
While serving as a special assistant to the baseball operations department of the Cleveland Indians, on June 8, 2011, Pérez was named hitting coach of the Miami Marlins, replacing John Mallee, a position he held until manager Ozzie Guillén and most of his staff were let go shortly after the 2012 season. He managed the team representing Colombia in the World Baseball Classic Qualifying Round in 2013, finishing with a 1–2 record.[23]
He served as the Houston Astros bench coach under manager Bo Porter during the 2013 season. For 2014, he was named the Astros first base coach, but he resigned that position in early January 2014 to spend more time with family.[24]
On February 11, 2014, ESPN announced that Pérez had rejoined the network as a studio and game analyst.[25]
During the winter of 2014–2015, Pérez served as the manager of the Santurce Crabbers in the Puerto Rican Winter League. The Crabbers won the league championship and participated in the Caribbean World Series.
Pérez is married to Mirba Rivera; they wed in December 2000. The couple has two daughters–Andreanna, born in 2003, and Juliana, born in 2006. The family's main residence is in San Juan, Puerto Rico. The family now lives in Miami, Florida.[28][23]