On a 1-2 offering from Nationals right-hander Shairon Martis in the fourth inning, Cantu connected on a solo homer to left-center. It was the third baseman's 25th blast of the season.
The Marlins became the first team in Major League Baseball history to boast four infielders with at least 25 homers apiece.
Cantu joins first baseman Mike Jacobs (32), second baseman Dan Uggla (30) and shortstop Hanley Ramirez (29) as the first foursome to achieve the benchmark. Upon reaching the dugout after his historical blast, the first three to greet Cantu were none other than Jacobs, Uggla and Ramirez.
"It's something that is really hard to do," Cantu said. "Twenty-five home runs is not easy to do in the big leagues. For four to be able to do that is unbelievable. I don't know how else to describe it. It's amazing. It's such a great feat. I'm going to be talking about it 30 years from now. My grandkids and kids, we can tell we were the first to do that.
"It was just a matter of time. The way we were swinging the bats, it was going to happen."
Cantu's homer loomed large as it helped the Marlins pull out a 2-1 win over the Nationals.
Marlins manager Fredi Gonzalez says the foursome should be somehow recognized by the Hall of Fame in Cooperstown, N.Y.
"We were all so excited for him," Gonzalez said. "They will go down in history. These guys have got their names in the Hall of Fame. It should be. This was big, and I'm glad to be part of it."
Of all the great infields in the history of the league, the Marlins achieved the feat with a relatively young infield. Cantu, 26, is in his fourth season, while Ramirez (24), Uggla (28) and Jacobs (27) are all in their third, full big league seasons.
For Cantu, who should be a strong candidate to win Comeback Player of the Year, the 25 homers are three shy of his career high of 28 set while he was with Tampa Bay in 2005. He hadn't hit more than 14 in the big leagues since then.
Typically, 25-home run power comes from corner infielders. But the Marlins have two of the most dynamic hitting middle infielders in the game.
"The guys up the middle [in years past] were there for defense," Jacobs said. "They weren't in there for driving in runs and hitting homers. Obviously, the game has evolved. You've got guys who hit homers. I think [former second baseman Alfonso] Soriano was one of the first guys who played up the middle and was hitting homers."
Cantu has played mostly third base this season, but he's also seen considerable action in the late innings at first base.
In Cantu, the Marlins got a steal. He was a non-roster invitee to Spring Training, who was brought in to help replace slugger Miguel Cabrera, who was traded last December to Detroit.
"Here's a guy who was a Spring Training invitee," Gonzalez said. "We gave him an opportunity to compete for a job, and he won that job. I think he's been the most consistent hitter we've had all year."
The foursome has already taken some pictures together in anticipation of the achievement, and Cantu is hoping to get the ball.
Uggla said he wants the photo to recognize the achievement.
"It's crazy. I was happy for [Cantu]," Uggla said. "To have something like that weighing on him is not fun. It feels great. Any time you do something that has never been done before, always make it a little special."
Home runs have been a staple of the team. Counting outfielder Cody Ross' 21 homers, the Marlins have five players with more than 20 homers for the first time in their history.
The Marlins have never had three players reach 30 in a year. Ramirez is on the brink of doing that.
A year ago, three Florida infielders had more than 25 homers: Cabrera (34), Uggla (31) and Ramirez (29).
In all, eight teams in history have had three infielders with 25 or more: Marlins ('08), Marlins ('07), Rangers ('05), Diamondbacks ('05), Rangers ('04), Rangers ('03), Yankees ('02) and Dodgers ('79).
"It's good to be part of this," Ramirez said. "It's a big honor to have our names as a part of that. I'm so happy right now."
Joe Frisaro is a reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.