"Following a meeting between Olympiakos's major shareholder Vangelis Marinakis and Ewald Lienen, it was agreed that his contract should be terminated by mutual consent," the club said on their official website.
Olympiakos lost 1-0 to Maccabi Tel Aviv on Thursday and were beaten in the third qualifying round on the away goals rule. Lienen's only other competitive game during his 53 days in charge was the 2-1 win over Maccabi in the first leg.
The 56-year-old had left German side TSV 1860 Munich to coach Olympiakos in June.
"There was a lot of pressure on me and the team and I have decided to leave by mutual consent," Lienen told reporters.
"It was a short but very nice experience for me. Olympiakos is a big team with great facilities and I wish the new owner and the club good luck for the future."
Marinakis, who took over ownership of the club shortly after Lienen was hired, said that a new manager would be hired "within the next few days."
"We are going to get a very good manager," he told reporters. Spaniard Ernesto Valverde, who led Olympiakos to the Greek league and cup double in 2009 is the favourite to succeed Lienen.
