The Department of Corrections says the first phase of transfers began just after 9 a.m. Wednesday from the state prison at Graterford to the sprawling, $400 million complex at SCI Phoenix.
Several hundred inmates will be moved each day by bus, for however long it takes to complete the operation.
A spokeswoman says the roads between the facilities, about 35 miles (56 kilometers) northwest of Philadelphia, are closed to the public during the transfer.
The new prison can house about 3,830 male inmates. It also has a separate, 192-bed female transition unit outside the perimeter.
Pennsylvania has 25 state prisons after closing three in the last five years.