Officials in northeastern Pennsylvania say the river is projected to crest at 41 feet between 4 p.m. and 8 p.m. - the same height as the levee system protecting riverfront communities. Residents were ordered to leave by 4 p.m.
The evacuations come as the remnants of Tropical Storm Lee dumped heavy rain and caused havoc around the Northeast, bringing floods that cut off major highways and caused some schools to open late or not at all.
Two rain-related deaths were reported in Pennsylvania. Police in Derry Township said a man who was removing water from his basement was killed when the house's foundation collapsed, and a motorist trapped in a vehicle drowned early Thursday morning in Elizabeth Township, in Lancaster County.
Flood watches and warnings were in effect from Maryland to New England.
In Philadelphia, flooding and a rock slide closed the eastbound lanes of the Schuylkill Expressway, a major artery into the city, and it could take hours for the road to reopen.
In New York, the Thruway Authority expected to close a 105-mile stretch of Interstate 90 where it runs along the Mohawk River, which had overflowed its banks in some areas. It's the state's most heavily traveled east-west highway.
The National Weather Service predicted rain would continue to fall heavily across the mid-Atlantic and Northeastern states through Thursday with anywhere from 4 to 7 more inches falling and up to 10 inches in isolated pockets.
The Associated Press contributed to this report.