Leoluca Orlando spoke as the patrol vessel Niamh arrived with 370 survivors of Thursday's disaster and 25 corpses, including the bodies of children.
Orlando called on European leaders to do more to prevent such disasters and to allow more refugees to settle in their countries.
The mayor said that a new generation of mafia mobsters was planting roots in Italy due to the EU's failure to allow migrants to enter Europe legally and find work.
Orlando, who is credited with breaking the hold of Cosa Nostra, the Sicilian mafia, on Palermo's regional Government during his 30-year political career, said the system was feeding "organised crime, death and violence" by forcing migrants to operate outside the law.
Illegal migrants who arrive in Italy across the Mediterranean, and who are subsequently unable to rent a house or find a job while they wait for asylum applications to be processed, are regularly "exploited" by the mafia, he said.
Some 224,000 migrants and refugees have crossed the Mediterranean to Europe so far this year, the United Nations said yesterday. That number is already higher than the total for the whole of 2014, when 219,000 people made the journey.
EU commissioners called on Europe to find the "collective courage" to keep promises made in May after a similar shipwreck claimed the lives of 800 migrants: "Migration is not a popular or pretty topic. It is easy to cry in front of your TV set when witnessing these tragedies.
"It is harder to stand up and take responsibility," they said.
In addition to expanding EU naval operations, the commission will hold a November summit in Malta with key African countries from which migrants travel.
Italy has repeatedly pleaded for more EU resources to manage the growing migrant crisis unfolding on its shores. Separately, the Italian navy yesterday rescued 381 migrants from another fishing vessel in distress 30 nautical miles off Libya.
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