The 34-year-old - who joined PSG on a free transfer from Barcelona during the off-season - collected 613 points to finish ahead of Bayern Munich's Robert Lewandowski (580) and Chelsea's Italy midfielder Jorginho (460) at a star-studded ceremony in Paris.
The Argentinian superstar claimed a maiden Copa America title with his country this year and was the top scorer in La Liga for the 2020-21 season with 30 goals as Barcelona finished
He added to his 2009, 2010, 2011, 2012, 2015 and 2019 Ballon d'Or trophies, while five-time winner Cristiano Ronaldo was voted sixth best for 2021.
"It's incredible to be here again. Two years ago I thought it was the last time. Winning the Copa America was key", Messi said after collecting the award.
Messi helped Barcelona win the Copa del Rey last season before moving to PSG in the summer.
Lewandowski, 33, who was widely expected to win last year, scored 38 goals in 30 league games for Bayern Munich in 2021 and 11 goals in 12 games for Poland.
He netted in 19 consecutive games in all competitions for Bayern from February to September and he just missed out on equalling the record of scoring in 16 Bundesliga games in a row.
"I would like to say to Robert that it's an honour to be your rival, and everyone would say you deserved to win it last year," Messi said.
Awarded by France Football magazine, the Ballon d'Or has been awarded since 1956 when Stanley Matthews won.