The Pope said migrants often met "rejection from those who could offer them welcome and assistance".
He also condemned terrorism as "a blind and brutal violence" that should be fought with "weapons of love".
The Pope was delivering his "urbi et orbi" (To the city and the world) message to thousands amid tight security in St Peter's Square.
The Pope said: "The Easter message of the risen Christ... invites us not to forget those men and women seeking a better future, an ever more numerous throng of migrants and refugees... fleeing from war, hunger, poverty and social injustice.
"All too often, these brothers and sisters of ours meet along the way with death or, in any event, rejection by those who could offer them welcome and assistance."
Tens of thousands of migrants, mainly fleeing conflict in Syria and Iraq, are now stranded in Greece, after European nations and Turkey agreed a plan to shut their route to northern Europe.
Pope Francis also offered a prayer for Syria: "The risen Christ points out paths of hope to beloved Syria, a country torn by a lengthy conflict with its sad wake of destruction, death, contempt for humanitarian law and the breakdown of civil concord."
He expressed his hope for success at peace scheduled to resume next month.
The Pope also urged people to use the "weapons of love" to combat the evil of terrorism.
He spoke of recent attacks in Belgium, Turkey, Nigeria, Chad, Cameroon, Ivory Coast, and Iraq.
"May [the risen Jesus Christ] draw us closer on this Easter feast to the victims of terrorism, that blind and brutal form of violence which continues to shed blood in different parts of the world," he said (text in Italian).
The latest terror attack - in Brussels on Tuesday - left 28 people dead. The former king and queen of Belgium, Albert II and Paola, attended the Mass on Sunday and met the Pope.
Many pilgrims cancelled their planned trips to Rome in the wake of the violence in Brussels, but the square was packed on Sunday, as was St Peter's Basilica when Pope Francis celebrated Mass on Saturday evening.
In his homily in the basilica, he called on Christians not to let fear and pessimism "imprison" them.
He said: "Today is the celebration of our hope. It is so necessary today."

Goals in either half from Jackson Irvine and Brian Graham earned them all three points.
Motherwell's late response began with Stephen Pearson's fierce strike.
But Scott Fox saved from James McFadden and brilliantly kept out a Keith Lasley drive to frustrate Motherwell.
It was a pulsating finish to a game that only sparked into life when Irvine fired in the opening goal.
The Australian was only drafted into the starting line-up minutes before the match because of an injury in the warm-up to Martin Woods.
And he made a great case for his inclusion when he deftly controlled a deep corner before lashing the ball past Connor Ripley, despite the best efforts of Kieran Kennedy on the line.
Fox saved well from a Louis Moult header and Chris Cadden as Motherwell tried to mount a swift response, but County regained the ascendancy at the start of the second half.
Playing principally on the counter-attack, they went close on a number of occasions, with Michael Gardyne having a header cleared off the line and passing up another great chance with a low drive that was blocked.
They got the second goal their play deserved when Graham slotted past Ripley as the Motherwell defence failed to deal with a Stewart Murdoch cross.
That looked like game over until Pearson's late strike - the midfielder blasting past Fox from 12 yards.
But the keeper was sharply off his line to prevent McFadden's lob beating him and he sprung to his right to deny Lasley a spectacular equaliser.
The result leaves Motherwell just a point above the relegation play-off spot and County in good spirits ahead of next weekend's League Cup semi-final against Celtic.
Pope Francis has condemned those who fail to help migrants, during his traditional Easter speech in Rome.
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Ross County survived a late onslaught from Motherwell for their first league win of 2016, moving them up to fourth in the Premiership.