Cantu originally signed as a 16 year-old free agent with the Tampa Bay Devil Rays in 1998 out of Reynosa, Mexico. He would bounce around the Rays minor league system for six seasons before getting his shot in 2004, hitting .301 in 50 games after a mid-season call up.
Cantu showed Major League power in 2005, hitting 28 homers and 117 RBI while hitting .286 as a regular part of Tampa Bay's lineup, splitting time between second and third base.
Injuries limited Cantu to 107 games in 2006, as he hit a disappointing .249 with only 14 home runs and 62 RBI. After appearing in only 25 games through July of 2007, and hitting .207 with zero home runs, he was traded with Shaun Cumberland and cash to the Cincinnati Reds for Calvin Medlock and Brian Shackelford.
Cantu again underperformed for the Reds, in 27 games only managing one home run while hitting .298. Cincinnati granted his outright release after the season ended. The Marlins signed him off the scrap heap 13 days later for relative peanuts.
Cantu made the opening day roster out of spring training in 2008 when Jose Castillo was claimed off waivers by the San Francisco Giants. He was so impressive during spring training that he was named the Marlins starting third baseman. He also showed his versatility, filling in at third base as needed for the Marlins. He belted a career-high 29 home runs along with 95 RBI, posting a .277 average.
In 2009, Cantu amassed 16 home runs along with 100 RBI, hitting .289, again splitting time between third and first base.
Cantu totalled 55 home runs and 249 RBIs, hitting .278 in 401 games with Florida.