Messi, who helped to steer Argentina to Copa America glory in July and was named Player of the Tournament in the process, beat Bayern Munich's Robert Lewandowski to the most prestigious individual prize in world football.
The 34-year-old has now won the award at back-to-back ceremonies, having also been named the world's best player in 2019, while the 2020 awards were cancelled due to the coronavirus pandemic.
Messi's tally of seven Ballons d'Or is now two clear of his perennial rival Cristiano Ronaldo, who finished sixth in the voting - outside the top three for the first time since 2010.
Chelsea - winners of the inaugural Club of the Year award - boasted two players in the top five following their Champions League triumph.
The Spain international finished well clear of Borussia Dortmund's Jude Bellingham and Bayern Munich's Jamal Musiala, while Nuno Mendes and Mason Greenwood made up the top five, with Bukayo Saka making it three English players in the top six.
Lewandowski scooped a new prize for Striker of the Year to partially make up for his runners-up finish in the main award, while Barcelona's Alexia Putellas took home the Women's Ballon d'Or gong ahead of teammate Jennifer Hermoso and Chelsea's Sam Kerr. body check tags ::