The 32-year-old, who lifted the trophy in 2009, 2010, 2011, 2012 and 2015, beat Liverpool's Champions League winner Virgil van Dijk in a vote of international journalists.
Messi won Spain's Liga title with Barca this year and led Argentina to third place at the Copa America in July.
The United States midfielder Megan Rapinoe has won the women's Ballon d'Or award after helping her country to retain the World Cup in France this year.
The 34-year-old was the driving force behind the US team that claimed a record-extending fourth world title in July.
Rapinoe was not present at the ceremony in Paris to collect football's most prestigious individual accolad.
"I'm so sad I can't make it tonight. It's absolutely incredible congrats to the other nominees. I can't believe I'm the one winning in this field, it's been an incredible year," Rapinoe said in a recorded message.
"I want to thank my team mates and the U.S. federation."