He played in Major League Baseball (MLB) from 1987 through 2000 for the Oakland Athletics, Florida Marlins, Colorado Rockies, and Atlanta Braves.

Although the Series would be overshadowed by the Loma Prieta earthquake on October 17 which delayed play for ten days, Weiss homered and the A's swept the Giants to claim their first world title in fifteen years.

In what would be his final year in Oakland, he hit .212 in 1992 and was traded to the new NL expansion Florida Marlins for Eric Helfand and a player to be named later during the offseason.

In December 1997, he signed[5] with the Atlanta Braves and became their starting shortstop, hitting .280 and making the 1998 All-Star team[6] for the only time in his career.

The Braves finished with 106 wins but lost the NL pennant to the San Diego Padres, although he was slowed by injuries and appeared in less than a hundred games for the first time since 1991.

While with the Braves, Weiss's family had a health scare when his 3-year old son contracted E. Coli from an Atlanta water amusement park which caused his kidneys to shut down.

In the bottom of the tenth, with the bases loaded, one out and the score tied, Tony Eusebio hit a sharp grounder up the middle.

[12] Weiss, while serving a bench coach for the Atlanta Braves, won a World Series Championship in 2021 after defeating the Houston Astros 4 games to 2 on November 2, 2021.

[citation needed] On October 21, 2022, Weiss was offered an interview for the Miami Marlins vacant managerial position, but turned down the opportunity.