The Frenchman left Spurs in October 2008 after the departure of manager Juande Ramos and joined St Etienne, whom he has now left to move to Anfield.
"Damien has a proven track-record of identifying exciting young footballing talent and we are delighted that he has agreed to join Liverpool," said John Henry, principal of New England Sports Ventures - the club's new owners.
"Working closely with Roy Hodgson and the coaching staff, I know he will make a valuable contribution to strengthening the club and the squad as we move forward.
"Today's announcement is just the first step in creating a leadership group and structure designed to develop, enhance and implement our long-term philosophy of scouting, recruitment, player development and all of the other aspects necessary to build and sustain a club able to consistently compete at the highest level in European football.
"We intend to be bold and innovative. We will not rest until we have restored Liverpool Football Club to the greatness Liverpool fans expect."
Manager Roy Hodgson believes the squad he inherited from predecessor Rafael Benitez was lacking quality in depth and has complained about his options on the playing front several times this season.
Comolli's appointment is intended to help the Reds boss boost his squad with the right type of player.
"I am looking forward to working with Damien whom I have known for many years," said Hodgson.
"We are engaged in an exciting project here and he will bring a lot to the table.
"We all want to see moves to strengthen the squad and support player development over the next few years. John Henry and I are totally united in delivering on that ambition."
Comolli added: "I am delighted to be joining Liverpool and look forward to working with John and Roy.
"I think we all realise there is a big job ahead, but we all share the vision that John has for rebuilding the club and bringing back the success that the supporters deserve."