The San Diego Padres confirmed the news Monday in a Twitter release, but did not give a cause of death.
Gwynn had battled salivary gland cancer, the result of his longtime use of chewing tobacco. He had surgery to remove a malignant tumor in 2009 and again in 2012.
"We are terribly sad to say goodbye to our teammate, our friend and a legend, Tony Gwynn," the Padres said. "Rest in peace, Mr. Padre."
Gwynn was inducted into the Hall of Fame in 2007, having been selected on 97.6 percent of ballots. He spent his entire 20-season career with the Padres, winning eight National League batting titles and earning 15 All-Star selections.
A career .338 hitter, Gwynn batted better than .350 seven times, including a career-best .394 during the strike-shortened 1994 season. He never hit below .309 in a full season and finished his career with 3,141 hits.
"For more than 30 years, Tony Gwynn was a source of universal goodwill in the National Pastime, and he will be deeply missed by the many people he touched," said baseball commissioner Bud Selig in a statement. "On behalf of all of our clubs, I extend my deepest condolences to Tony's wife Alicia, their son Tony Jr. of the Phillies, their daughter Anisha, the Padres franchise, his fans in San Diego and his many admirers throughout baseball."
Gwynn helped the Padres to a pair of World Series appearances -- first in 1984 and again in 1998. He was 8-for-16 during the four-game sweep by the Yankees in '98.
After his playing career ended in 2001, Gwynn returned to his alma mater at San Diego State and was the head baseball coach since 2003. He had been on medical leave since March and had just signed a contract extension with the Aztecs last week.