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.