The highways impacted are Interstates 95, 76, 476, 676 and Route 1.
They will be closed from 7:00 p.m. Monday until at least 2:00 a.m. Tuesday.
That word came hours after the city announced that schools, public transportation and trash pickup will still be shut down as Hurricane Sandy makes its way toward Philadelphia.
The School District of Philadelphia, as well as Archdiocesan Schools, will be closed again on Tuesday.
Philadelphia Mayor Michael Nutter also announced that there will be no trash pickup on Tuesday in Philadelphia. Residents will have to hold onto their trash until next Tuesday.
There will also be no SEPTA service on Tuesday morning. SEPTA officials will monitor the situation through the day and make decisions as the storm progresses.
More than 250 people had already evacuated to shelters in the Philadelphia area by daybreak Monday - hours before Hurricane Sandy's worst was even expected to make landfall.
Sheila Gladden evacuated from her home in Philadelphia's flood-prone Eastwick neighborhood and headed to a hotel, preferring not to take any chances.
"I'm not going through this again," said Gladden, who had five-and-a-half feet of water in her home after Hurricane Floyd in 1999.
"They're telling me this is going to be worse than Floyd because this is some superstorm," she said. "I'm not going back until the water's receded."
Mayor Michael Nutter told Action News early Monday that shelters are open and ready to help those who have to get out.
"If you have not relocated, if you are in one of those areas, the time to go is now, because things are only going to deteriorate as time goes on," Nutter said.
"We're going to all have to hang in there together."
The city remains under a state of emergency until 5:00 p.m. Tuesday.
Mass transit service was shut down, all flights were canceled out of Philadelphia International Airport and Amtrak stopped service.
Meanwhile, the Delaware River Port Authority said bridges would be closed to truck traffic at 2:00 p.m. Monday. Those bridges are the Commodore Barry, the Walt Whitman, the Ben Franklin and the Betsy Ross.
Also, the DRPA said the Commodore Barry Bridge will be closed to all traffic when sustained winds (not just gusts) reach 50 m.p.h.
Earlier Monday, the Pennsylvania National Guard activated 750 soldiers and expects to have a total of 1,600 placed on active duty to deal with damage caused by Hurricane Sandy.
Guard spokesman Staff Sgt. Matthew Jones says 50 guardsmen had already been on duty since Friday and 800 more based in Pittsburgh and Scranton expect to be activated by noon Monday.
The National Weather Service issued high wind and flood warnings for much of southeastern Pennsylvania, where winds of up to 75 mph and up to 10 inches of rain were possible.
Officials warned Sandy is a dangerous storm that promises to bring power outages that could last for days and cause rain-swollen waterways to rise over their banks.
Gov. Tom Corbett declared a state of emergency in anticipation of storm damage while utility companies called in reinforcements to deal with what could be massive power outages.
Officials are warning residents of flood-prone areas - like those affected by the remnants of Hurricane Irene last year - to be ready to move.
In Philadelphia, the American Red Cross has set up emergency shelters Saturday at three schools that are expected to be opened Sunday beginning at 4:00 p.m.
West Philadelphia High School
4901 Chestnut Street
Roxborough High School
6498 Ridge Avenue
Samuel Fels High School
5500 Langdon Street
(All open at 4pm Sunday)