Benfica came second in Portugal last year but in December failed to qualify for the Champions League knock-out rounds, and after defeats to modest clubs now sit fourth in the domestic league.
On Wednesday the side scored two own goals in a 2-0 defeat to Portimonense.
“Benfica have come to an agreement with Rui Vitoria for an immediate end to his contract,” the club said in a statement on Thursday.
Benfica’s ‘B’ team coach Bruno Lage, has been appointed as an interim coach.
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