He was raised in his father's hometown and began to play baseball, with his father as coach, at age six. Known by the nickname "Sandino," he played Little League baseball while he attended elementary school and was a member of the Luis Muñoz Rivera High School baseball team.
He signed with the San Diego Padres in 1984 and went through the minors for seven years until he joined their major league team in 1988. After going over to the Cleveland Indians in 1990 he was named the American League's Rookie of the Year unanimously by The Sporting News, Baseball America, USA Today, Sports Illustrated, and CNN. That same year he became the first rookie catcher ever to start the All-Star Game and won a Rawlings Gold Glove. His second season with the Cleveland Indians was plagued with injuries; however, he managed to put together his first career four-hit game and threw out 30 percent of base runners trying to steal base. In 1992 he started in his third consecutive All-Star Game and was the first Cleveland Indian to start three straight midsummer classics since 1946.
By 1994 he improved his record of tossing out base runners attempting to steal to 35 percent. However, he had another season marked by numerous injuries and underwent arthroscopic surgery on his knee. Although the recovery was slow at times, in 1995 he enjoyed two two-homer games in Texas and Minnesota. The year 1997 was one of his most solid seasons with the Indians. He appeared in 127 games, the most since his rookie year, and for the first time he did not spend any time on the disabled list. He hit a career-best 17 straight games between April 11 and May 4.
Until 1997, Alomar Jr. seemed to walk in his younger brother's shadow when it came to field statistics, as it took him a year longer them his younger brother Roberto to make it to the big leagues. But 1997 was his best season ever. For the first time he caught in 100 games back-to-back and had the highest hitting average in his career: .324 (37 doubles, 21 homers, and 83 RBIs). He became the first Cleveland Indian to ever win the MVP (most valuable player) of an All-Star Game and the first player to win the MVP in his home park. The Indians were in the World Series that year and Alomar Jr. became the fifth player ever in World Series history to have 10 or more RBIs (runs batted in) in a single series. He also became the first player in major league baseball to homer in his home park in the World Series and in the All-Star Game. His success that year earned him a spot on the Wheaties Cereal box. He has been plagued with injuries since 1998 and once again underwent knee surgery in May 1999. Until 1999 he had the fourth-highest number of career grand slams, at 855.
During the 2000 season, Alomar Jr. had a 30-game hitting streak, the second longest ever by a catcher, and by the end of that season, he was a lifetime 276 hitter with 93 home runs and 459 RBIs. After eleven seasons with the Indians and unsuccessful off-season contract negotiations with Cleveland, Alomar Jr. signed with the Chicago White Sox in April 2001.