The Los Angeles Dodgers superstar needed one stolen base and two home runs to achieve the feat and took his tally to 51 home runs and 51 steals during a 20-4 win over the Miami Marlins.
The 30-year-old stole third base in the first inning to achieve the first part of the record.
He then added another steal to move to 51, before smashing a 49th home run of the season in the sixth inning.
That home run tied the Dodgers’ record for most in a season set by Shawn Green in 2001.
The Japanese player then made it 50 in the next inning to become the first player to record the 50-50 feat.
“To be honest, I’m the one probably most surprised,” Ohtani said.
“I have no idea where this came from, but I’m glad that I performed well.”
Reacting on X, formerly Twitter, NFL superstar Patrick Mahomes of the Kansas City Chiefs described Ohtani’s achievement as “insane”, while basketball icon LeBron James said “This guy is unreal! Wowzers”.
‘One of a kind’ Ohtani on course to be ‘best ever’
Ohtani joined the Dodgers on a 10-year $700m (£527m) contract – the biggest deal in the sport’s history – in December after leaving the Los Angeles Angels.
It made him one of the highest-earning athletes in the world.
MLB ambassador and former World Series winner Chase Utley told BBC Sport Ohtani is “truly one of a kind”.
“To do it in his first year in a Dodgers uniform is pretty special. He has separated himself – I don’t think there is a question – as the best [current] player in all of baseball,” Utley said.
“If he continues this pace throughout the course of his contract he will go down as the best player to ever play the game. You couldn’t have dreamed of a season like that.
“He can really do it all. You don’t see a player who has the ability to hit the ball over the fence but also steal that many bases.
“He is the first to do it and I can’t imagine many are going to do it any time soon – I’m not sure I see it happening ever, to be honest.”
Ohtani has played 866 MLB games, the most among all active players to have never played in the post-season until now, after the Dodgers made the play-offs for a 12th straight year.
MLB commissioner Rob Manfred said: “While Shohei Ohtani has been a groundbreaking player for many years, his latest feat as the first 50-50 player in the history of Major League Baseball reflects not just his amazing power-and-speed talent, but his character, his drive, and his commitment to all-around excellence.
“On behalf of Major League Baseball, I congratulate Shohei on this remarkable achievement. We are proud that he continues to take our game to new heights.”
BBC Sport will have live coverage of Sunday’s game between the Baltimore Orioles and Detroit Tigers, a crucial game in the play-off race, on BBC iPlayer, plus the BBC Sport website and app, from 18:30 BST, with coverage beginning on the Red Button at 19:30.
