Brosius became one of the limited number of players to hit a home run in his first major league game, on August 7, 1991. Brosius was the A's starting third baseman through the mid-1990s, although he played almost 300 games in his Oakland career at other positions, primarily in the outfield. In 1996, he batted .304 with 22 home runs, his best year with Oakland; however, his performance declined in 1997 when he became the last player to finish last in the majors, of those who qualified for the batting title, in batting average, on-base percentage, and slugging average. He was traded to the Yankees after the season for Kenny Rogers, who had struggled mightily in New York.
In his first year in the Bronx, he batted .300 with 19 home runs and 98 RBIs. That season, he was selected to his only career All-Star Game. He hit .471 with two homers and six runs batted in in the 1998 World Series, and was named the Most Valuable Player. He hit 2 home runs in Game 3 of the World Series, including one off of Padres closer Trevor Hoffman to give the Yankees a 3-0 Series lead.
Although his performance over the next three years did not match that of his 1998 season, he remained a perennial fan favorite in the Bronx; his workmanlike blue-collar approach and serviceable durability appealed to fan, teammate, and management alike. During his career with the Yankees, they won the American League pennant every year, from 1998 to 2001, as well as the World Series from 1998 to 2000. He won a Gold Glove in 1999. On July 18 of that year, against the Montreal Expos, Brosius caught Orlando Cabrera's foul popup for the final out of David Cone's perfect game. He was first among all AL third basemen in errors in 2001, with 22, and had the lowest fielding percentage in the league (.935).
In the most dramatic clutch moment of his career, Brosius hit a two-out, two-run home run in the bottom of the ninth inning of Game 5 of the 2001 World Series against the Arizona Diamondbacks to tie the game and set up an extra-inning Yankees win. The previous night, New York first baseman Tino Martinez had hit a two-out, two-run home run to tie the game in the ninth as well. It marked the first time in World Series history that this had ever occurred. The Yankees would go on to lose Games 6 and 7 of the series, after which Brosius retired.
From 2002 to 2007, Brosius was an assistant coach at Linfield College under head baseball coach Scott Carnahan, Brosius's coach when he played for the school. In 2007, Carnahan became athletic director and Brosius was named head coach. He earned his degree from the school in 2002. As a coach Brosius has been named NWC coach of the year twice in three seasons as head coach and led the team to two World Series appearances including a 3rd place finish in 2010. In 2013 Brosius and The Wildcats won their first Baseball national championship.