In Houston, Bagwell blossomed, becoming one of the best players in Astros franchise history. Bagwell spent his 15-year career in a Houston uniform and, along with teammate Craig Biggio, was synonymous with the Astros throughout the 1990's and into the 2000's.

The best year in Bagwell's professional career was the strike-shortened 1994 season when he was unanimously named National League. He became the first National Leaguer to finish first or second in batting average, home runs, RBI, and runs scored since Willie Mays in 1955. His .750 slugging percentage in 1994 was the highest by a National Leaguer since Rogers Hornsby in 1925. Bagwell won an MVP award in 1994. 

Bagwell was also considered a strong fielder, winning a Gold Glove award in 1994, and compiling a career .993 fielding percentage. He also exhibited above-average speed and baserunning skills for a first baseman, stealing 202 bases over his career, including two seasons in which he stole at least 30 bases, and five seasons in which he stole at least 15.

In 1997, Bagwell became the first full-time first baseman to steal 30 bases while hitting 30 home runs. The Houston Astros retired his number 5 jersey on August 26, 2007.