Biggio was an All-American baseball player at Seton Hall University, where he played with other future Major League Baseball stars Mo Vaughn and John Valentin. He was drafted by the Houston Astros in the first round (22nd overall) in 1987.
Biggio was called up as a catcher midway through the 1988 season and became the Astros starting catcher and won the Silver Slugger award in 1989. Biggio was a very speedy runner and an adept base stealer. Astros' management, in an attempt to keep the rigors of catching from sapping Biggio's speed, tried him in the outfield part-time in 1990. The Astros finally convinced Biggio to convert to second base in spring training 1992, even though Biggio had made the All Star team as a catcher in 1991. Biggio made the All Star team for the second time in 1992, becoming the first player in the history of baseball to be an All Star at both catcher and second base. Biggio became known as a reliable, hustling, consistent top of the order hitter, with unusual power for a second baseman. His stats reflect this, having consistently good marks in hitting, on-base percentage, hit-by-pitch, runs, stolen bases and doubles throughout his career.
His consistency was epitomized by playing 1,800 games without ever being put on the disabled list until August 1, 2000, when he had a season-ending knee injury. In the play that Biggio was injured on, the Florida Marlins' Preston Wilson slid into second base, trying to break up a double play, and hit Biggio's planted left leg, tearing the anterior cruciate ligament and medial collateral ligament in Biggio's knee. Biggio rebounded with a good season in 2001, but had a lackluster performance in 2002, with only a .253 average, his lowest since entering the league. However, he improved slightly for the 2003 season, averaging .264 with 166 hits despite being asked by management to move to centerfield. In 2004, he put up numbers more typical for his career, batting .281 with 178 hits, including 24 homers. Biggio moved to yet another new position, left field, midway through the 2004 season to accommodate Carlos Beltrán. Biggio moved back to his favorite position, second base, in 2005, and set a career high in home runs with 26.
Biggio led the majors in runs scored in 1995 and 1997 and in doubles in 1998 and 1999. In 1997, he became one of the few players in baseball history to not hit into a single double play all season. He tops the Astros' career list in games played, at-bats, runs scored, hits and doubles. By the end of the 2005 season, Biggio had 2,795 hits, 604 doubles, 260 home runs, 1,063 RBIs, and 407 stolen bases. His accomplishments with the bat are all the more impressive for having played his best years in the Astrodome, a notorious pitcher's park. He is also known as a 'killer B' (originally with teammates Jeff Bagwell, Derek Bell, and Sean Berry and more recently Bagwell, Lance Berkman, and Carlos Beltrán (2004)). (Beltran has since signed with the New York Mets.) Biggio is gaining momentum as a likely future Hall of Famer. Baseball writer Bill James in the Revised Historical Abstract rated Biggio at the 4th best second baseman of all time and the 35th best player of all time, making a detailed argument that throughout his career, Biggio has been a better player than Ken Griffey, Jr..
On June 29, 2005, Biggio broke the post-1900 career hit by pitch (HBP) record, previously held by Don Baylor with 267. In the fourth inning of a game against the Colorado Rockies at Coors Field, a pitch from Byung-Hyun Kim hit Biggio on the left elbow for his 268th HBP. He is currently the active leader in this category with 273, only 14 behind Hughie Jennings. On October 19, 2005, his Houston Astros beat the St. Louis Cardinals in the National League Champonship Series, enabling Biggio to participate in the World Series for the first time in his career. On October 25, Biggio became the first Astros player to hit and score a run in a World Series home game.