"For some months now, we have witnessed an event which fills us with hope: the process of normalising relations between two peoples following years of estrangement," said Francis in a speech on the tarmac of Jose Marti International Airport.
"I urge political leaders to persevere on this path and to develop all its potentialities as a proof of the high service which they are called to carry out on behalf of the peace and well-being of their peoples, of all America, and as an example of reconciliation for the entire world."
Francis did not explicitly mention human rights in his speech but said he would pray for all Cuba, "that it may travel the paths of justice, peace, liberty and reconciliation".
The pontiff's speeches in Cuba are being closely watched for their handling of two delicate and related topics: human rights in Cuba and the church's freedom to operate in the officially agnostic, communist state.
After being greeted at the airport by Raul Castro, Francis was due to rest for the remainder of the day ahead of his first big Mass on Sunday in Havana's Revolution Square, an official meeting with the Cuban president, a vespers service and his first encounter with Cuba's young people.
"The people and the Government of Cuba welcome you with profound affection, respect and hospitality," President Raul Castro told him in a long welcome speech.
After flying from Cuba to the US on Tuesday he will, like his predecessors, grab the world stage at the United Nations to press his agenda on migration, the environment and religious persecution.
Elsewhere in the US, Francis will be delivering the message that Hispanics are the bedrock of the American church.