Reed Johnson was called out on a force play following a bunt, but the umpires reviewed the ruling and determined third baseman Kyle Seager had juggled the ball. The Mariners then deployed five infielders, and Stanton cleared them all with a towering homer to the left of the home-run sculpture.
Stanton had five RBIs to increase his total to 26, most in the majors.
The Mariners lost their fourth game in a row, while the Marlins won for only the second time in the past 11 games.
Johnson singled to start the ninth against Yoervis Medina (0-1), and Christian Yelich beat out a sacrifice bunt for his third hit. Marcell Ozuna's bunt loaded the bases following the replay review, and Stanton hit his sixth homer on a 1-2 count.
Jarrod Saltalamacchia hit his second homer for the Marlins, who won despite two errors that led to three unearned runs.
The Marlins' Nathan Eovaldi pitched six innings and allowed three runs, one earned. He lowered his ERA in seven interleague starts to 1.70.
Steve Cishek (1-0) pitched a perfect ninth.
The Mariners, beginning their first series in Miami since 2005 and their second ever, squandered repeated scoring chances. They went 2 for 11 with runners in scoring position.
Abraham Almonte had a double and a triple and scored twice, but slumping Robinson Cano went 1 for 5 and is 4 for 22 on the Mariners' trip.
The Mariners' patchwork rotation again failed to go deep into a game. Chris Young lasted only three innings while giving up seven hits and four runs.
A miscue by Marlins right fielder Stanton led to two unearned runs. The Marlins have allowed 14 unearned runs this season, and they came into the game tied for the most in the majors.
The Marlins also overcame some bad baserunning, a problem since the season started. Yelich was an easy out trying to score from second on a two-out infield hit, and Saltalamacchia was picked off first.
Miami scored twice in the first on run-scoring singles by Stanton and Casey McGehee. Stanton went 3 for 3 and was intentionally walked twice.
The Marlins went ahead 3-2 in the second on a sacrifice fly by Ozuna.
The Mariners twice erased two-run deficits, and they tied the game in the seventh with an unearned run. Miami second baseman Derek Dietrich's fourth error of the season extended the inning, and Corey Hart took advantage with a two-out RBI single.
Seattle took advantage of sloppy defense by Miami in the second inning. With Michael Saunders on first, Dustin Ackley singled to right. Stanton charged the ball and it hopped over his glove and rolled to the warning track, and both Saunders and Ackley scored.
Almonte led off the fifth with his first triple and scored on Brad Miller's groundout.
NOTES: Seattle OF James Jones made his big-league debut when he came off the bench in the seventh inning, and he singled in the eighth. ... Yelich extended his hitting streak to 12 games. ... McGehee is 8 for 15 (.533) with runners in scoring position. ... Eovaldi needed 13 pitches to retire Hart in the first inning. ... Marlins manager Mike Redmond, a Seattle native, grew up a Mariners fan and said he probably attended their home opener 15 years in a row. ... LHP Roenis Elias (1-1, 2.16), who earned his first major league win in his most recent outing, is scheduled to start Saturday for Seattle against Henderson Alvarez (0-2, 4.30). Alvarez turned 24 Friday.