Padilla was selected by the Philadelphia Phillies in the third round of the 1998 Major League Baseball Draft. He soon made his debut with the Rookie-level Martinsville Phillies. He batted .356 with five homers and 25 RBIs in 23 games.
In 1999 Padilla split his season between the Class A Piedmont Boll Weevils, where in 44 games he hit .208 with three homers and 17 RBIs, and the Short-season Batavia Muckdogs, where in 65 games he hit .252 with three homers and 30 RBIs.
With the Class A Clearwater Phillies Padilla ranked ninth in the South Atlantic League in batting with a .305 average. He also had 11 home runs and 67 RBIs in 108 games in 2000.
He spent the entire 2001 season with Class A Advanced Clearwater, hitting .260 with 16 homers, 66 RBIs and 23 stolen bases in 100 games.
In 2002 Padilla was promoted for the Double-A Reading Phillies. He hit .256 with seven homers, 65 RBIs and 32 stolen bases in 127 games.
Playing for Double-A Reading again in 2003, Padilla batted .295 with two homers and 23 RBIs. He suffered a hand injury in late June, which required season-ending surgery.
With the Triple-A Scranton-Wilkes Barre Red Barons Padilla batted .253 with seven homers and 45 RBIs in 117 games in 2004.
Padilla started the 2005 season with Clearwater after missing two months with an injury. He soon rejoined Triple-A Scranton-Wilkes Barre. He got off to a great start hitting .317 in his first 19 games but fell apart in his final 30 games batted .223.
In 2006 Padilla spent the entire year with the Double-A Binghamton Mets marking his first season in the New York Mets organization. He hit .295 with 10 homers and 54 RBIs in 129 games. Padilla finished fourth in the Eastern League in hitting and third in hits with 142. He was selected for the Eastern League All-Star team.
He spent the 2007 season with the Double-A Wichita Wranglers in the Kansas City Royals organization. He hit .336 with 10 homers, 51 runs scored and 49 RBIs in 69 games and was soon promoted to the Triple-A Omaha Royals where he hit .291 with six homers, 27 runs scored and 20 RBIs in 55 games.
Padilla hit .330 with a homer, 25 runs scored and 14 RBIs in 33 games with the Double-A Harrisburg Senators. This marked his first season in the Washington Nationals organization.
He started the 2009 season with the Syracuse Chiefs.
Padilla was called up to the Nationals after right fielder Austin Kearns was placed on the disabled list with a right thumb contusion. Padilla earned the promotion after hitting .367 with four home runs and 21 RBIs for the Triple-A Syracuse Chiefs. The right-handed hitter stated his reason for his high batting average was his ability to hit the ball to the opposite field.
On August 22, Padilla got his first start in left field for the Nationals.
After becoming a free agent following the 2009 season, Padilla signed with the Toronto Blue Jays. On June 18, 2010, he was traded to the New York Mets for future considerations. On November 10, 2010, Padilla became a minor league free agent.
The San Diego Padres signed free-agent OF Jorge Padilla (Marlins) to a minor league deal Wednesday, May 30.
Was released from San Diego Padres Organization July 3, 2012
Padilla was once married to Sheila Gonzalez. Padilla is a 1998 graduate of Florida Air Academy in Melbourne, Florida. He was first-team All-State in baseball in 1997–98 and Player of the Year.