He played in Major League Baseball as a catcher for the Oakland Athletics (1985), Milwaukee Brewers (1987–90), New York Mets (1990–93), Atlanta Braves (1994–95), Toronto Blue Jays (1996–97), Chicago White Sox (1998), Anaheim Angels (1998–99) and Montreal Expos (2000).

During his tenure with the Braves, O'Brien was notable for being the personal catcher for Baseball Hall of Fame pitcher Greg Maddux.

The Athletics traded O'Brien with Steve Kiefer and minor leaguers Mike Fulmer and Pete Kendrick to the Milwaukee Brewers for Moose Haas.

He batted .324 with 15 home runs and 74 RBI with the El Paso Diablos of the Class AA Texas League in 1986.

[3] He began the 1991 season as the starting catcher, ahead of Mackey Sasser[4] and served as a backup to Todd Hundley when the latter was promoted.

He signed with the Chicago White Sox for the 1998 season in order to share the catching position with Chad Kreuter,[8] but was traded to the Anaheim Angels for minor leaguers Brian Tokarse and Jason Stockstill in July 1998.

[12] Over the course of his career, O'Brien caught eleven different Cy Young Award winners: Frank Viola, Dwight Gooden, Bret Saberhagen, David Cone, Greg Maddux, Tom Glavine, John Smoltz, Pat Hentgen, Roger Clemens, Chris Carpenter and Jack McDowell.