Shohei Ohtani, the Los Angeles Dodgers' Japanese superstar, had staked the National League to a 3-0 lead with a three-run blast in the top of the third.
But the AL scored five unanswered runs to win the Midsummer Classic for the 10th time in 11 years, rebounding at Globe Life Field in Arlington, Texas, after dropping last year's edition 3-2 in Seattle.
Duran earned All-Star Most Valuable Player honors as the AL denied the NL's bid to win a second straight for the first time since they won three in a row from 2010-2012.
It was tied at 3-3 with one runner on base and two out when Duran crushed the second pitch he saw from Cincinnati starter Hunter Green to right center field.
"I know he throws really hard so I was like, alright, I hope he throws me a fastball first pitch so I can see how hard it is. And then he just gave me a pitch to put a good swing on," Duran said.
The 27-year-old was playing in his first All-Star Game after the first half of the season saw him set career highs with 10 home runs and 41 runs-batted-in to go with 22 stolen bases.
"I can't really put into words right now," Duran said as he accepted the MVP trophy named for legendary hitter Ted Williams. "I'm kind of overwhelmed with emotions, but I'm just very thankful to be here and to represent the Red Sox is big honor."
Ohtani had electrified the crowd of more than 39,000 at the home of the Texas Rangers with a 400-foot blast into the right field seats off an 88 mph splitter from Tanner Houck.
The blast was the Japanese star's first All-Star Game homer in his fourth appearance.
His previous three came for the AL when he played for the Los Angeles Angels, including a 2021 appearance when he got the win on the mound.
Ohtani inked a record $700 million free agent deal with the Dodgers before this season, and his homer was the first All-Star home run by a Dodger since Mike Piazza's in 1996.
Ohtani's homer also scored Jurickson Profar, who hit a leadoff single, and Ketel Marte, who reached on an error by American League and hometown second baseman Marcus Semien.
But the AL answered with three runs in the bottom of the third.
Juan Soto's double up the middle scored Semian and Steven Kwan, then Soto scored on a single by Cleveland's David Fry.
Skenes sizzles
Pittsburgh rookie Paul Skenes, who was named an All-Star and got the starting nod despite having made just 11 starts in his two months in the major leagues, pitched a hitless first for the NL, delivering two 100 mph pitches.
He walked Juan Soto, but then struck out Soto's New York Yankees teammate Aaron Judge to end the inning.
He threw 11 of 16 pitches for strikes, mixing a fastball that twice hit 100 mph with his trademark "splinker" pitch, a sinker and splitter hybrid.
"It was cool to face off against them back-to-back,” Skenes told broadcaster Fox of taking on Soto and Judge. "They were tough."
The 22-year-old, who was the first rookie pitcher to start an All-Star Game since Dodgers sensation Hideo Nomo in 1995, had retired Cleveland outfielder Kwan -- whose batting average of .352 leads MLB -- and Gunnar Henderson to open the game.
