Trains generally run along the Northeast Corridor between Boston in the north to Washington, D.C., in the south with multiple stops, including in New York City, Philadelphia, and Baltimore.

Extensions and branches provide service to Newport News, Norfolk, and Roanoke, Virginia, and Springfield, Massachusetts, with intermediate stops.

On October 28, 1995, Amtrak introduced the "NortheastDirect" brand for all trains on the Northeast Corridor (and its extension to Newport News, Virginia) except for the express Metroliner and hourly Clocker services.

The first two all-electric round-trips to and from Boston were branded Acela Regional and equipped with refurbished Amfleet cars painted in the Acela-like "Phase V" livery.

"[12] As part of rebranding and service improvements, the name was changed to "Northeast Regional" on June 23, 2008 (though it also appeared on schedules several months beforehand).

[18][19] They were temporarily cancelled north of New York City effective April 4, 2023, due to Penn Station Access construction.

[21] One daily Northeast Regional round trip was extended to from Washington to Lynchburg via Manassas and Charlottesville on October 1, 2009, supplementing the existing Crescent service.

[25] On July 20, 2010, Amtrak added an additional Northeast Regional frequency from Washington to Richmond Staples Mill Road station, increasing the Washington-Richmond corridor to eight daily round trips with hourly northbound morning service.

Romaine said that Amtrak wanted the extension, in part, due to Ronkonkoma's location next to Long Island MacArthur Airport.

Northeast Regional trains operating south of Washington, D.C., into Virginia, and on the New Haven–Springfield Line use GE Genesis diesel locomotives which have a slightly lower top speed of 110 mph (180 km/h).

The arrangement will offer a near-seamless transition between power sources on through trains to Virginia and Springfield, Massachusetts, a process that currently requires a time-consuming locomotive change.

All classes of service include complimentary WiFi, an electric outlet (120 V, 60 Hz AC) at each seat, reading lamps, and fold-out tray tables.

[41] Some trips diverge at New Haven and turn north to serve Springfield, Massachusetts, operating over Amtrak's New Haven–Springfield Line.

[3] Several trips continue south of Washington D.C. to Virginia, running to either Roanoke, Richmond, Newport News, or Norfolk.