Meares made his major league debut on May 5, 1993 with the Minnesota Twins. He played six full seasons with the Minnesota Twins, with a high of 152 games in 1996. He was granted free agency after the 1998 season, and he then signed with the Pittsburgh Pirates before the 1999 season. He played two full seasons and one incomplete season (1999 with 21 games) with the Pittsburgh Pirates with a career high of a .308 batting average in 1999. Meares played 742 games with the Minnesota Twins and 239 games with the Pittsburgh Pirates, with a total of 981 professional baseball games in his career. His last major league game took place on October 7, 2001 vs. Chicago Cubs.