US President Barack Obama welcomed the pope as he landed on Tuesday – a rare honour for a foreign dignitary.
The pontiff will visit Washington DC, New York and Philadelphia.
Before he departed Cuba on Tuesday, he called on its people to live a “revolution of tenderness”.
In the final Mass of his four-day visit to the island, with President Raul Castro attending, he urged thousands of Cubans to serve one another and not an ideology.
On the trip from Cuba to the US, the Pope held a news conference and answered those who said his criticisms of capitalism went too far.
A large delegation including the Obama family greets Pope Francis as he arrives at Andrews Air Force Base in Maryland
The Pope will visit the Oval Office on Wednesday
“I’ve never said anything that is not in the social doctrine of the church,” the Pope told reporters. “Maybe I have given the impression of (being) a bit lefty, but that would be a mistaken interpretation.”
When he landed at Andrews Air Force Base, the Pope was greeted by Mr Obama and his family along with Vice-President Joe Biden and his wife.
The crowd, which included a military honour guard, schoolchildren, politicians, and Roman Catholic clergymen, chanted: “Welcome to the USA! Hello! Hey!”
After a brief chat with Mr Obama, the pope rode away in a small charcoal-gray Fiat as part of a motorcade bound for the Vatican diplomatic mission in Washington.
Authorities have launched one of the biggest security operations in US history to ensure the pope’s safety.
The pontiff, who has sought to bring Catholics back to the church with a more inclusive message, is very popular in the US and is expected to draw massive crowds in all three cities.
A large portion of central Philadelphia will be practically closed off during his visit and federal employees in Washington have been urged to work remotely while the Pope is in the capital.
The event could attract up to a million and a half people.
The Pope enjoys going into crowds and using an open-sided Jeep rather than a bulletproof “popemobile”, throwing US law enforcement off as they mount huge security operations.
The BBC’s Will Grant in Cuba says the Pope has avoided any overt political statements during his visit there but commentators say he is expected to be more outspoken while in the US.