The 46-year-old Filipino retired four years ago but will compete for the WBC welterweight title at the MGM Grand on July 19th.
"I’m back," he posted on social media. "On July 19, I return to the ring to face WBC Welterweight Champion Mario Barrios at the MGM Grand in Las Vegas."
Pacquiao has recently been involved with politics in his native Phillippines, serving as a senator between 2016 and 2022 before launching an unsuccessful bid for presidency.
The Filipino star returns to boxing where he won 62 of his 72 bouts, with 39 of them coming via knock-outs.
He lost his WBA title by unanimous decision to Yordenis Ugas in 2021, but was recently handed a fifth-place ranking by the WBC allowing him to challenge Barrios for the belt.
Barrios, who has a 29-32 record, beat Ugas to win the WBC interim belt in 2023 and retained his WBC welterweight belt against Abel Ramos in Texas last November.
Two-time WBA champion Amir Khan was sparring partner for Barrios and told Sky Sports he "deserves" the fight.
"It's a fantastic fight for Mario, he needs that big fight. He'll be paid well and fighting a legend like Manny Pacquiao, who would say no to that?" he said.
"Mario deserves this fight because every fighter wants that big payday. It will be fantastic for him.
"He's a very good boxer. I don't know how much Manny's got left in him. If they were in their prime, in their peak, then I'd say all day Manny Pacquiao. But this could be a tricky fight for Pacquiao."