Wilkerson played college baseball for the University of Florida, and was selected by the Montreal Expos in the first round of the 1998 MLB draft.

During his major league career, Wilkerson played for the Montreal Expos / Washington Nationals, Boston Red Sox, Texas Rangers, Seattle Mariners, and Toronto Blue Jays.

In the 1996 College World Series, he hit a dramatic grand slam to defeat the rival Florida State Seminoles.

As a junior in 1998, he became the first player in college history to hit 20 home runs, steal 20 bases, and win 10 games as a pitcher in the same year.

For the season, Wilkerson played in 129 games combined between Harrisburg and Ottawa, batting .295 with 18 home runs, 79 RBIs, and 47 doubles in 441 at-bats.

[8] While coming up through the minors, Wilkerson was a member of the gold medal-winning USA baseball team in the Sydney Olympics.

Wilkerson made his major league debut with Montreal on July 12, 2001 against the Tampa Bay Devil Rays.

He appeared once more in an Expos uniform during the Major League Baseball Japan All-Star Series shortly after the 2004 regular season.

Wilkerson opened the 2005 season as the regular center fielder and leadoff hitter after the Expos moved to Washington and became the Nationals.

[16] On December 7, 2005, Wilkerson was traded to the Texas Rangers along with outfielder Terrmel Sledge and minor league pitching prospect Armando Galarraga for second baseman Alfonso Soriano.

[23] On February 16, 2009, Wilkerson signed a minor league contract with an invitation to spring training with the Boston Red Sox.

[24] He is one of the few players to play both major league Canadian teams, the Toronto Blue Jays and the Montreal Expos.