McKeon's resignation had been expected, and he confirmed it to the team in the clubhouse before the game.
"He got very emotional when he told us, like your granddad is going away and you're not going to see him anymore," veteran Jeff Conine said. "It's tough for him. Baseball is his life."
McKeon led the Marlins to the 2003 World Series title and a winning record in each of his three seasons as manager. Now 74, he said he told his family last year that this season would be his last, and he decided almost two months ago to keep that pledge. But he didn't rule out managing again.
(Dontrelle) Willis said he was saddened by McKeon's decision to resign.
"He's a great baseball mind," Willis said. "But he wants to get with his family, and you've got to respect that."
The third-oldest manager in major-league history, McKeon will remain with the Marlins as an adviser -- and he's open to offers from other teams.
"Sometimes you need to step back and maybe take a breather for six or seven months and get recharged," he said. "I haven't given up the thought of managing again."
McKeon, who began his managerial career in the minors 50 years ago, became the 52nd manager to earn 1,000 major-league wins Sept. 3. Three of the Marlins' four winning seasons came since he came on board in May 2003.
"He taught our organization to work hard," general manager Larry Beinfest said. "That set the tone for all the good things that happened to us."
Beinfest said the team will likely wait until after the World Series to hire a replacement.