Ausmus was a standout athlete in high school, being named the Avon Old Farms Player of the Year in his senior season; he was a teammate of National Hockey League defenseman Brian Leetch on the Connecticut high school baseball championship team in 1984. Ausmus chose an unusual route to the major leagues: he played minor league baseball during the summers while attending Dartmouth College, from which he graduated with a A.B. in government. He also served as a volunteer coach and bullpen catcher for the Big Green.

He was drafted by the New York Yankees in 1987 and selected by the Colorado Rockies in the 1992 expansion draft but did not appear in a major league game for either team. He also played for the San Diego Padres and Detroit Tigers. In 2004, Ausmus hit .248 with five home runs and 31 RBI in 129 games. He hit his second career postseason home run in Game 1 of the National League Division Series against Atlanta. He has caught at least 100 games in all of his 11 full major league seasons, and ranks fourth among active catchers in games played (1,443). He is the active leader in career RBI (461 through 2004) among former Ivy Leaguers. His best season offensively was 1999 with the Tigers, where he batted .275 with 9 home runs and 54 RBIs, the last two being career highs.

In Game 4 of the 2005 NLDS against the Atlanta Braves, Ausmus homered with two outs in the bottom of the ninth to tie the game at 6-6 and send it to extra innings; the Astros eventually won in the 18th inning of the longest postseason game in major league history.

Ausmus and his wife Liz reside in San Diego with their daughters Sophie and Abigail.