NOAA/AP Photo

As millions of people begin their travel plans for the Thanksgiving holiday some of the nation’s largest cities will be pounded with severe weather that could potentially cause major delays on highways and at airports as two major storms hit the Northeast and Northwest.

Forecasters say some of the worst weather in the country for mid-week  will be on the coasts and could back up some of the busiest airports such as those in Boston, New York City, Philadelphia, Washington, D.C., San Francisco and Seattle.

“The roads and the airports are going to be extremely busy, this is on a per day basis the busiest travel holiday of the year.  42.5 million Americans will travel 50 miles or more from home this weekend,” Troy Green of the American Automobile Association said.

The National Weather Service reports an active weather pattern for the East Coast, with a front moving through the Ohio Valley and Mid-Atlantic and onto New England.

“As this system moves toward New England on Wednesday, it will bring a wintry mix of precipitation, with a mixture of snow and freezing rain possible from upstate N.Y. into upper New England. Total snow accumulations of 4 to 8 inches,” the NWS said.

And approximately 90 percent of the 42.5 million Americans traveling Wednesday will be doing so by car — many of them driving directly into a storm.

Along the East Coast the issue facing most travelers will be the rain, which will lead to minor flooding, gusty winds and heavy snow across northern New England. The areas around Burlington, Vt., Concord, N. H. and into Portland and Augusta, Me., will be hit particularly hard.

“Wet, slick conditions can make the trip a little bit longer as people are taking precautions as they’re headed to their destinations,” Green said.

The good news on the East Coast however is that the rain will end by mid to late morning so the afternoon will be dry with sunshine. Snow and wind will linger through the afternoon in northern New England and Coastal Maine.

A total of 12 counties in the Portland, Maine area are now under advisories, watches, or severe weather warnings , ABC News’ Portland, Maine affiliate WMTW reported.

From Washington to Oregon and into northern California major winter storms with flooding are expected, as are damaging winds, heavy mountain snow and possibility of mudslides and avalanches.

Cities expected to be impacted during Wednesday’s travel rush include Seattle, Portland, with San Francisco getting the rain by afternoon.

A powerful cold front brought wind gusts over 70 mph to Seattle, according to ABC News affiliate KOMO. Strong winds knocked out power to thousands across the region, with Puget Sound Energy reporting about 10,000 customers without service.

A fresh storm is expected to come into the Seattle area on Thanksgiving Day, bringing a round of heavy rain, wind and snow.

As for air travel, the weather can still affect those flying, so the best advice is to get to the airport early and try to get in the air as early as possible.

As of 7 a. m. there were only 66 flights cancelled — the bulk of which were at Newark Liberty, New York’s LaGuardia, Washington D.C.’s Reagan and Philadelphia International. Philadelphia is the only airport with any delays of note — departure delays are currently running a little over an hour there.

“Book the earliest flights possible, because flight delays tend to reverberate throughout the system as the day progresses,” Green says. “So not only are you dealing with that with inclement weather, you have to factor in the time it’s going to take you to get through security.”