The Pope has expressed his sorrow over the sacking of Constantinople by Catholic crusaders in 1204.
It was the Patriarch's first Vatican visit in nine years
His comments came during a visit by the spiritual leader of some 300 million Orthodox Christians, Patriarch Bartholomew I of Constantinople.
The city - now Istanbul - was sacked by the crusaders to pay debts.
The Pope said he welcomed the patriarch to the Vatican with "joy" and hoped for a healing in the long rift between Eastern and Western Christianity.
"We are praying that the Lord of history purifies our
memories of every prejudice and resentment and allows us to
freely proceed on the road of unity," he said.
He referred to the "painful episodes of history" which had cast a shadow over their relationship.
"In particular, we cannot forget what happened in the
month of April 1204," he said.
"How can we not share, at a distance of eight
centuries, the anger and the pain."
Relations between the Catholic and Orthodox churches have undergone renewed tension over claims the Catholics are trying extend their influence in the traditionally Orthodox countries of the former Soviet Union.
The Pope has previously apologised for sins committed by Catholics against Orthodox Christians, for the Crusades themselves, and to Jews for anti-Semitism.
Patriarch Bartholomew was at the Vatican for the first time in nine years.
The Pope remains keen to visit Russia, but Russian Orthodox Patriarch Alexiy II has refused to sanction the move.