The most notable flop has been 35 million-pound striker Andy Carroll, who joined from Newcastle United as a replacement for Fernando Torres in January 2011.
Stewart Downing and Jordan Henderson have also flattered to deceive.
"I think it's fair to say no supporter would be delighted with the results we've achieved this year," Liverpool chairman Tom Werner told the club website.
"We're coming close to the end of the season and the transfer window for the summer, and we felt it was important to make this change expeditiously."
Once mighty Liverpool face city rivals Everton in the FA Cup semi-final this weekend and won the League Cup this term but lie eighth in the Premier League.
Comolli, a former Arsenal scout who later became director of football at Tottenham Hotspur, joined Liverpool in November 2010 to oversee player recruitment after the U.S.-based Fenway Sports Group had taken over the five-times European champions.
Werner said they were looking for a replacement but team manager Kenny Dalglish was not under threat.
"We're still confident the structure we've discussed is the right structure. That doesn't mean we won't look at tweaking it, but we feel a collective group of people making football decisions is healthy," he said.
"We've got great confidence in Kenny. We feel the team is going to make strides in the future and he enjoys our full support."
Comolli, who also had stints at Saint-Etienne, made his name thanks to successes at Tottenham where he signed Welsh winger Gareth Bale from Southampton and midfielder Luka Modric from Dinamo Zagreb.
"I am grateful to have been given the opportunity to work at Liverpool and am happy to move on from the club and back to France for family reasons. I wish the club all the best for the future," Comolli said.
