But Sheffield's milestone was significant not only for the exclusive club it allowed him to join and the circumstances in the game. The 40-year-old slugger became just the third player in history to hit home runs before turning 20 years old and after turning 40. The other two are Hall of Famer Ty Cobb and Rusty Staub. Sheffield also joins Hall of Famer Jimmie Foxx as the only two players to hit their 500th home runs against their original teams. Foxx hit his in 1940 while playing for the Red Sox against the A's.
Sheffield, the 25th member of the 500 Home Run Club, also became the first player to reach that plateau in a Mets uniform and to do so while getting his first hit for a new team.
Here's a look at some of the other significant home runs Sheffield hit on his road to 500.
Home run No. 1
Much like his latest long ball, Sheffield's first had a significant impact on the game. The 19-year-old rookie shortstop for the Brewers hit his first Major League home run off of Seattle's Mark Langston in the sixth inning on Sept. 9, 1988, at Milwaukee's County Stadium. It was his first Major League hit, and it broke up Langston's bid for a no-hitter. Best of all for the Brewers, it tied the game at 1, and they went on to win, 2-1, in 11 innings.
Two teams and nearly six years later, Sheffield reached the century mark as a Marlin. He hit his 100th home run on Aug. 10, 1994, off of the Cardinals' Omar Olivares at Miami's Joe Robbie Stadium.
Three months after the Marlins traded Sheffield to the Dodgers, he was back in Miami on Aug. 20, 1998. He hit No. 200 against Florida's Rafael Medina.
On July 21, 2001, Sheffield and the Dodgers were in Denver to play the Rockies. Home run No. 300 came in the fifth inning off of Denny Neagle to break a 5-5 tie and No. 301 came in the sixth off of Dan Miceli.
Sheffield's 400th home run came after he returned to the American League. Playing for the Yankees in Toronto, Sheff homered off of Mike Nakamura on July 27, 2004.
Sheffield has said repeatedly that, other than 500 home runs, the number he focused on during his career was 493 -- the total hit by fellow Tampa, Fla., native Fred McGriff. On Sept. 1, 2008, Sheff passed his pal while playing for the Tigers, sending a pitch from the Yankees' Sidney Ponson over the wall at Comerica Park.
Dan Cichalski is an editorial producer for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.