The 2010 award came five years after his last triumph and capped a year of unprecedented club success in which he also extended his scoring record at the African Nations Cup finals.
The Cameroon captain finished ahead of Ivory Coast's Didier Drogba and Asamoah Gyan of Ghana in the polling for Africa's top individual prize, awarded at the Confederation of African Football's awards gala in Cairo.
"It is a pleasure to be a winner again, to take it for the fourth time against such top opposition," Eto'o told a news conference after the ceremony.
"It is true now that Africa has so many good players and there is lots of talent coming up, so this might be a last chance for me."
Eto'o was African Footballer of the Year from 2003-05 and his fourth award surpasses the three titles won by Abedi Pele in the early 1990s.
Eto'o's goal-scoring form helped Inter Milan to a triple of titles last season, including the UEFA Champions League in which the 29-year-old took a winner's medal for a second successive year.
He scored on Saturday as the Italians beat African champions TP Mazembe Englebert in the Club World Cup final in Abu Dhabi.
Eto'o scored twice at the Nations Cup in Angola in January to stretch his tournament record tally of goals to 18. He also netted at the World Cup finals but later described Cameroon's poor performance in South Africa as the biggest disappointment of his career.
