He faces unspecified charges in connection with a payment his lawyer made to porn star Stormy Daniels before the 2016 presidential election.
The trip began as he emerged from Mar-a-Lago in front of supporters cheering him on. It could end with a more hostile crowd lining the streets of Manhattan.
Here's a more detailed guide on what to expect from each leg of his journey.
Step one - from beachfront residence to airport
The former president, a New York native, currently resides at Mar-a-Lago, his sprawling beachfront residence and members-only club in Palm Beach, Florida.
He left home around 12:20 local time (17:20 BST).
Mr Trump is being accompanied by US Secret Service agents. One official who spoke on condition of anonymity told the Washington Post that "dozens and dozens" of agents would be required to ensure the trip is secure.
He travelled in a motorcade to Palm Beach International Airport, which is 2.5 miles (4km) from Mar-a-Lago. He has used the airport many times before and it's about a 15-minute drive.