The 25-year-old Argentinian took the honour ahead of Barcelona team-mate Andres Iniesta and Real Madrid striker Cristiano Ronaldo.
Messi enjoyed a remarkable 2012 even by his own high standards, most notably surpassing Gerd Muller's 40-year-old record of 85 goals in a calendar year, finishing with an incredible 91.
Messi said: "To tell you the truth this is really quite unbelievable. The fourth award that I have had is just too great for words.
"I would like to recognise my other colleagues from Barcelona; Andres it has been great to train and play alongside you.
"I would also like to recognise all of my friends in the Argentinian national team, everyone that has worked with me, coaches and staff and my family and my friends. Also my wife and my son. Thank you."
Messi polled 41.60 per cent of the votes, with Ronaldo taking 23.68 per cent and Iniesta 10.91 per cent.
Although he missed out on both La Liga and Champions League crowns, he racked up a host of personal achievements last year.
He scored an unprecedented 50 goals in a La Liga season, a record 14 goals in a Champions League season and became the first player to net five times in a Champions League match.
He also shattered the myth that he does not perform as well for Argentina as he does for his club by scoring 12 goals for his country in nine games.
Messi's fourth award takes him past the three won by both former Brazil striker Ronaldo and former France midfielder Zinedine Zidane.
Speaking at the pre-gala press conference, Messi claimed he did not consider 2012 his best year yet.
He said: "I'm more interested in team awards than I am about what I might win individually. There have been years where we won more titles that have been better."
Messi's team-mates and rivals paid tribute to him.
Barca midfielder Cesc Fabregas wrote on Twitter: "Congratulations Leo, forth time as the best player of #ballondor, you deserve it. And also to @andresiniesta8, huge to be there."
Argentina team-mate Sergio Aguero simply Tweeted: "Messi, Messi, Messi, Messi."
Manchester United defender Rio Ferdinand Tweeted: "Congrats to Messi! Wow,4 yrs in a row!! Messi has added something else to his list of 'the only person to....' #isMessiTheBestOfAllTime ??"
Fenerbahce's Miroslav Stoch won the FIFA Puskas Award for goal of the year, Spain boss Vicente Del Bosque was named World Coach of the Year and United States international Abby Wambach won Women's World Player of the Year.
The FIFPro World XI was named up entirely of players based in Spain with Barcelona's Dani Alves, Gerard Pique and Xavi, Real Madrid's Iker Casillas, Marcelo, Sergio Ramos and Xabi Alonso and Atletico Madrid's Radamel Falcao joining the three Ballon d'Or nominees in the team.
Franz Beckenbauer received the FIFA Presidential Award.
FIFA Ballon d'Or: Lionel Messi
FIFA Women's World Player of the Year: Abby Wambach
FIFA Men's Football Coach of the Year: Vicente Del Bosque
FIFA Women's Football Coach of the Year: Pia Sundhage
FIFA Presidential Award: Franz Beckenbauer
FIFA Fair Play Award: Uzbekistan FA
FIFA Puskas Award: Miroslav Stoch
FIFA/FIFPro World XI: Iker Casillas, Dani Alves, Gerard Pique, Sergio Ramos, Marcelo, Xabi Alonso, Xavi, Andres Iniesta, Lionel Messi, Radamel Falcao, Cristiano Ronaldo