The American Automobile Association said 38.3 million Americans will travel at least 50 miles from home, an increase of nearly 3 percent from last year.
And despite increasing prices for hotel rooms, rental cars and airfares, Triple-A expects airports and highways will be busier than ever.
Nearly 32 million travelers will be on the roads. They'll pay an average of $2.23 for a gallon of gas, about nine cents cheaper than a year ago.
Triple-A expects nearly five million people to travel by airplane, and almost two million by train, bus or another mode of transportation.
U.S. Airports will funnel through 25 million passengers this Thanksgiving and just a few slowpokes can derail the process entirely, CBS News correspondent Cynthia Bowers reports.
Complicating air travel are the new restrictions which allow passengers just 3 ounces of a liquid or gel to be carried in a one-quart bag.
The new rules are pushing toiletry makers to make more travel-sized items, said Marshal Cohen, chief analyst with The NPD Group Inc., a market research firm. That includes companies like Unilever, whose brands include Dove soap, and Procter & Gamble Co., which makes Pantene and other shampoos.
Roughly 10 percent of the industry now makes those sizes, said Cohen. He expects by the next holiday travel season that will reach 25 percent, driven by the new regulations.
"There are companies that are starting to recognize that this is something that is not going away," Cohen said.
Some airline counters will have baggies on hand for empty-handed passengers.
Phoenix Sky Harbor Airport started a similar effort in April 2004, handing out up to 10,000 bags a week, buying in bulk at a cost of 3 cents each, said spokeswoman Julie Rodriguez. Now with the new regulations, they're using 8,000 to 10,000 bags a day, she said.
Reporting from Chicago's O'Hare Airport, officials tell Bowers they expect more than two million people pass through O'Hare this week.
The Port Authority of New York and New Jersey predicted almost five million people would pass through local airports, bridges, tunnels and the PATH rail system between Wednesday and Sunday. To help handle traffic in the New York area, The Port Authority was to suspend non-emergency construction and maintenance work on the George Washington Bridge, the Lincoln and Holland tunnels and Staten Island's three bridges from Wednesday through Sunday.
Thanksgiving air travel was expected to surge, too. The Port Authority anticipated 1.6 million passengers — about 2 percent more than last year — would pass through LaGuardia, John F. Kennedy International and Newark Liberty International airports.
Meanwhile, the Homeland Security Department formally announced Wednesday that virtually all air travelers entering the United States after Jan. 23— even U.S. citizens. Until now, U.S. citizens, travelers from Canada and Bermuda, and some travelers from Mexico who have special border-crossing cards for frequent visitors were allowed to show other proofs of identification, such as drivers' licenses or birth certificates.
As for the weather Thanksgiving travelers can expect, rain and gusty winds will envelope most of the east coast. The south will be cool and dry with temperatures in the 50s and 60s. Meanwhile the Midwest should expect good weather, with temperatures up to the 70s. However, rain and possibly snow could dampen the northwest, according to Early Show meteorologist Dave Price.
Michael and Kathleen Chumer made their Thanksgiving getaway a day early, advancing smoothly Tuesday morning through curbside check-in at Liberty International Airport.
"I wouldn't leave on Wednesday," Kathleen Chumer said.
"It's going to be completely wacko," said her husband, Michael Chumer.
Triple-A's New York representative Robert Sinclair warned that drivers will face roads at their busiest between 3 p.m.-7 p.m. Wednesday and after 6 p.m. Sunday.
Since most travelers cannot avoid the heavy traffic times, Sinclair, who appeared on the CBS Early Show, advised that drivers make sure their tires and batteries are full — flat tires and dead batteries are the two biggest reasons for roadside assistance, he said.