The lefty-swinging Gwynn, nicknamed Mr. Padre, had a career .338 batting average, won eight National League batting titles and played in the franchise's only two World Series.
He died early Monday morning at Pomerado Hospital in Poway, California, while surrounded by his family, the Baseball Hall of Fame announced.
"Major League Baseball today mourns the tragic loss of Tony Gwynn," commissioner Bud Selig said in a statement Monday. "The greatest Padre ever and one of the most accomplished hitters that our game has ever known, whose all-around excellence on the field was surpassed by his exuberant personality and genial disposition in life.
"... 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."
Gwynn had been signed to a one-year contract extension as the baseball coach at San Diego State on Wednesday. He had been on medical leave since late March while recovering from cancer treatment. He took over the program at his alma mater after the 2002 season.
Survivors include his wife, Alicia, daughter, Anisha, and son, Tony Jr., who plays with the Philadelphia Phillies. Gwynn Jr., who is hitting .155 in 52 games this season, was put on the bereavement list Monday.
Today I lost my Dad, my best friend and my mentor. I'm gonna miss u so much pops. I'm gonna do everything in my power to continue to... - Tony Gwynn Jr. (@tonygwynnjr) June 16, 2014Make u proud! - Tony Gwynn Jr. (@tonygwynnjr) June 16, 2014He had two operations for cancer in his right cheek between August 2010 and February 2012. The second surgery was complicated, with surgeons removing a facial nerve because it was intertwined with a tumor inside his right cheek. They grafted a nerve from Gwynn's neck to help him eventually regain facial movement.
Gwynn had said that he believed the cancer was from chewing tobacco.
"He was in a tough battle and the thing I can critique is he's definitely in a better place," longtime agent John Boggs told The Associated Press. "He suffered a lot. He battled. That's probably the best way I can describe his fight against this illness he had, and he was courageous until the end."
In a rarity in pro sports, Gwynn spent his entire 20-year career with the Padres, choosing to stay rather than leaving for bigger paychecks elsewhere. His terrific hand-eye coordination made him one of the game's greatest contact hitters. He excelled at hitting singles the other way, through the "5.5 hole" between third base and shortstop.
"There are no words to express what Tony means to this organization and this community," the Padres said in a statement. "More than just Mr. Padre, Tony was Mr. San Diego. He cared deeply about our city and had a profound impact on our community.
"He forever will be remembered not only for his tremendous on-field accomplishments, but also for his infectious laugh, warm, outgoing personality and huge heart. On behalf of Padres fans everywhere, we mourn the loss of a friend, a teammate and a legend."
He was a 15-time All-Star and reached the coveted 200-hit mark in a season five times, and his .338 career average was 18th-best all time.
Gwynn hit safely in 1,838 games -- which amount to 75.3 percent of those in which he played. In addition, Gwynn had 951 multihit games, reached hitting streaks of at least 10 games on 33 different occasions and had only 34 multistrikeout games. In fact, he had only one career game with three or more strikeouts.
"I'll remember the cackle to his laugh. He was always laughing, always talking, always happy," said San Francisco Giants third-base coach Tim Flannery, who was both a teammate and a coach of Gwynn. "The baseball world is going to miss one of the greats, and the world itself is going to miss one of the great men of mankind. He cared so much for other people. He had a work ethic unlike anybody else, and had a childlike demeanor of playing the game just because he loved it so much."
Gwynn batted .300 in each of his last 19 seasons, an MLB streak second only to Ty Cobb's.
Gwynn was inducted into the Pro Baseball Hall of Fame in his first year of eligibility in 2007. His No. 19 was retired by the Padres in 2004, and a statue was erected in his honor at Petco Park.
"For more than a generation, the only thing more dependable in San Diego than sunshine was Tony Gwynn," Padres executive chairman Ron Fowler said. "No player ever has or ever will put on a Padres jersey without feeling the spirit and passion of #19."
Gwynn, who went into the Hall along with Cal Ripken Jr., was named on 532 of 545 votes cast (97.6 percent). He was also honored with the 1995 Branch Rickey Award, the 1998 Lou Gehrig Memorial Award and the 1999 Roberto Clemente Award.
"This is an extraordinarily sad day," Ripken Jr. said in a statement. "Tony was a Hall of Fame ballplayer but more importantly he was a wonderful man. Tony always had a big smile on his face and was one of the warmest and most genuine people I have ever had the honor of knowing. Like all baseball fans I will miss him very much and my thoughts are with his family today."
Gwynn homered off the facade at Yankee Stadium off San Diego native David Wells in Game 1 of the 1998 World Series and scored the winning run in the 1994 All-Star Game. He was hitting .394 when a players' strike ended the 1994 season, denying him a shot at becoming the first player to hit .400 since San Diego native Ted Williams hit .406 in 1941.
Gwynn befriended Williams, and the two loved to talk about hitting. Gwynn steadied Williams when he threw out the ceremonial first pitch before the 1999 All-Star Game at Boston's Fenway Park.
Several of baseball's former and current stars took to Twitter on Monday to post their thoughts on Gwynn, including Mike Piazza and Washington Nationals star Bryce Harper.
My Deepest prayers and condolences to the family of Tony Gywnn. No player carried himself with more class, dignity, and kindness. - Mike Piazza (@mikepiazza31) June 16, 2014Sad day in baseball..We lost one of the greatest hitters that ever played! Tony Gwynn you will be missed by many! Prayers out to his family!
- Bryce Harper (@Bharper3407) June 16, 2014Gwynn was a two-sport star at San Diego State in the late 1970s-early 1980s, playing point guard for the basketball team -- he still holds the school's game, season and career record for assists -- and outfielder for the baseball team.
Gwynn wanted to play in the NBA until realizing during his final year at San Diego State that baseball would be his ticket to the pros.
"I had no idea that all the things in my career were going to happen," he said shortly before being inducted into the Hall of Fame in 2007. "I sure didn't see it. I just know the good Lord blessed me with ability, blessed me with good eyesight and a good pair of hands, and then I worked at the rest."
He was a third-round draft pick of the Padres in 1981.
After spending parts of just two seasons in the minor leagues, he made his big league debut on July 19, 1982. Gwynn had two hits that night, including a double, against the Phillies. After doubling, Pete Rose, who had been trailing the play, said to Gwynn: "Hey, kid, what are you trying to do, catch me in one night?"
The Associated Press contributed to this report.
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