for a second time after agreeing a move to Benfica until June 2016.
Mitroglou joined Fulham from Olympiakos for £11m in January 2014, but has made just one start and two substitute appearances without scoring a goal.
The 27-year-old rejoined Olympiakos on loan last season, scoring 19 goals in 32 appearances.
"I didn't think twice when the opportunity arose," said Mitroglou.
The Greece international added: "I knew immediately that was where I wanted to go,
"I will try to score many goals for the team but the most important is to win the games. Of course, the goals are important for a striker and I am happy to play here."
Mitroglou won the Greek title and Greek Cup with Olympiakos last season, the 10th and 11th major trophies of his career.