Some 65,000 people were evacuated from Wilkes-Barre, a city in northeastern Pennsylvania, and another 35,000 people were evacuated in surrounding counties, authorities said. At least three people died in Pennsylvania due to the flooding.
Rivers and creeks already swollen by Hurricane Irene, which caused flooding in late August, threatened communities throughout the region thanks to torrential rain from a weather system that earlier soaked the U.S. Gulf Coast and tested the flood defenses of New Orleans.
About 20,000 residents of Binghamton, near the Pennsylvania border, were ordered to evacuate, New York Governor Andrew Cuomo said. There were more evacuations in Broome, Schenectady and Schoharie counties in New York, authorities said.
Residents of Havre de Grace, with a population of about 11,000, and other Maryland towns also were ordered to evacuate, authorities said. A state of emergency was declared in Pennsylvania's capital Harrisburg, hit by 12 inches (30 cm) of rain.
At Wilkes-Barre, the river was expected to crest at 40.7 feet (12.4 meters) later in the day and levies are built to withstand waters up to 41 feet (12.5 meters).
"Our number one priority is protecting lives and getting people out of harm's way," Luzerne County Commissioner Stephen Urban said.
In the Philadelphia area, flooding, mudslides and rock slides closed some of the busiest commuter highways, including the Schuylkill Expressway and U.S. Route 1, authorities said.
Railways were also shut because of flooding, including four heavily traveled commuter lines run by the Southeast Pennsylvania Transit Authority (SEPTA).
Amtrak shut rail service west of the New York capital Albany.
Weather forecaster Evan Myers said, "The combination of previous record rainfall, current tropical downpours from Lee, urban development and an already fragile watershed will lead to historic flooding in part of the Northeast this week."