On Monday, Jack McKeon's final series as manager of the Marlins began with a loss.
Michael Morse belted a three-run home run with two outs in the top of the ninth inning, sending the Nationals to a 6-4 decision.
Earlier in the day, the 80-year-old McKeon, interim manager of the Marlins, officially announced he will not return as skipper next season.
Marlins reliever Edward Mujica (9-6) worked himself into trouble from the start of the ninth. Pinch-hitter Laynce Nix and Ian Desmond singled, but Mujica struck out Rick Ankiel and induced a groundout from Ryan Zimmerman and could see his way out of the inning.
But he left a splitter out over the plate and Morse made him pay for it with his 30th homer, a shot to left-center.
Atahualpa Severino (1-0) pitched a scoreless eighth for his first major league win and Henry Rodriguez finished off the Marlins in the bottom of the inning to nail down his second save of the year.
Rick Ankiel had two RBI and Desmond scored three times for the Nats, who have won three in a row and eight of their last nine.
Vazquez, a veteran of 449 big-league outings, has been in prime form in his last five starts, winning all five while trimming his earned run average for the season by nearly a run and getting his record above .500.
He was 7-11 with a 4.67 ERA after a 3-1 loss at San Diego on Aug. 18, but got a no-decision in a Marlins win six days later and has subsequently won each assignment since -- defeating the New York Mets twice, Pittsburgh, Washington and Atlanta.
Vazquez allowed five hits in a complete-game blanking of the Nationals on Sept. 16 in Washington, walking none and striking out seven in Florida's 3-0 triumph.
He's not allowed a run over 22 innings in his last three starts and has given up only one in the last five overall - while allowing 19 hits and striking out 33 in 36 innings.
Vazquez is 3-2 in six career meetings with Washington.
The Nationals reply with lefty John Lannan, who aims for his 11th win of the season on his 27th birthday.
The Long Beach, N.Y. native was a 7-5 winner at Philadelphia in his most recent start after allowing three runs on eight hits in five innings.
The triumph gave him 10 in a season for the first time since he debuted with the Nationals with six late-season starts in 2007.
Lannan is 2-5 in nine career starts against Florida, including the 3-0 loss to Vazquez on Sept. 16.
The Marlins have won 10 of 16 over the Nationals this year.