Francis said the horrors of drug violence required "prophetic courage" from the church and a pastoral plan that involves families, parishes, schools and communities.
The pope said that the leaders have a duty to provide their people with indispensable material and spiritual goods.
Francis will meet with Mexican officials and foreign ambassadors at the National Palace in a moment.
He drove from the airport to the capital's south side in an open-air popemobile waving to the crowds lining the route.
Mariachis serenaded as his chartered plane pulled to a stop and people shouted "Brother Francis, you're already Mexican."
According to the papal agenda, President Enrique Peña Nieto and Pope Francis will hold a private meeting in a few minutes.
Mexican officials say the victims were bludgeoned, stabbed and hacked to death.
The declaration calls for peace in Syria, Iraq and Ukraine and urges Europe to "maintain its faithfulness to its Christian roots."
Trump says of the pope: "I don't think he understands the danger of the open border that we have with Mexico."
Here are five things to know about Francis' trip to the largest Spanish-speaking Catholic country in the world.