He had a very prosperous collegiate career and was part of a national championship team in his freshman year. He was selected with the 6th overall pick of the 1997 NBA Draft by the Boston Celtics and was reunited with Rick Pitino, his coach at Kentucky who had just become the coach of the Celtics. Prior to Mercer's drafting, Pitino was recorded as saying that he did not envisage Mercer as having the necessary talent to be selected very high. Some felt this was just a ploy to scare the other teams off of him so as to increase the likelihood of Mercer being available by the time the Celtics got an opportunity to make their draft selection.

After two seasons in Boston, Mercer was traded by the Celtics along with Popeye Jones and Dwayne Schintzius to the Denver Nuggets for Danny Fortson, Eric Williams, Eric Washington and a future draft choice. He played 37 games for Denver in 1999-2000, then played the final 31 games that year with the Orlando Magic due to a trade.

He left after that season, the next year signing as a free agent with the Chicago Bulls. He averaged 19.7 points per game in his first year with them. In his second season there he fared nearly as well, averaging 16.8 points per game, but he was traded partway through the season with Brad Miller, Ron Artest and Kevin Ollie to the Indiana Pacers for Jalen Rose, Travis Best, Norman Richardson, and a second-round draft pick. In Indiana he served merely as a role player, and his play declined rapidly.

Before the 2003-2004 season, he was traded to the San Antonio Spurs in a three-team trade that again involved Brad Miller and the Sacramento Kings' Hedo Türkoğlu. After playing 39 games with the Spurs, he was released. Prior to the 2004-2005 season, he signed with his seventh NBA team, the New Jersey Nets.