The American Automobile Association predicts nearly 60 million people will be doing some traveling of 50 miles or more, up 2.4 percent from last year.
Most of them — 81 percent — will drive, the auto club says, but about one in 7, or 8.3 million, will fly.
With the heightened national security alert, travelers were warned to leave extra time for getting through airports.
"In addition to that, people can do a lot to prepare to get through security more quickly. Simply things like making sure you don't have prohibitive items with you, like tools and pocket knives," TSA spokesman Mark Hatfield said on CBS News' The Early Show. "Don't wrap things before you get to the airport."
Officials also say to make sure you have photo identification with you and easily accessible. That's true for Amtrak trains as well as jetliners.
Lines were long at Washington's Seattle-Tacoma International Airport, but travelers told CBS radio affiliate KIRO-AM's Heather Bosch the lines were moving quickly.
"You deal with it, and I'd rather that be the case than not," said Mark Weaver, traveling through Seatac with his one-year-old daughter. "As long as everything's cool, as long as everything's safe, I can stay here as long as we need to."
Passengers had to wait up to 45 minutes to get through a single police checkpoint set up two miles from the Denver International Airport, DIA spokesman Steve Snyder said. Traffic backed up for at least two miles.
Police took steps Tuesday night to relieve the tie-ups at DIA, which is expecting 800,000 travelers this week, up from 730,000 last year.
"This is the first time we've been on an orange alert level with these kinds of numbers," Snyder said. "We were dealing kind of with an unknown situation."
For drivers, gasoline prices are about a dime higher than they were a year ago, at a national average of $1.48 for self-serve regular, but about 3 cents less than at Thanksgiving, AAA said.
Several state police agencies plan sobriety and seat belts checks and added patrols for the holiday weekend.
According to the travel club, the greatest number of Christmas-New Year's auto travelers will originate in the Southeast with 12.6 million; followed by the West, 12.1 million; Midwest, 9.9 million; Great Lakes, 7.7 million; and Northeast, 6.2 million.
The West and Southeast are expected to produce the largest number of air travelers, each with 2.4 million, followed by the Northeast, 1.6 million; Midwest, 1 million; and Great Lakes, 900,000.
And where are we going? Cities topped AAA's list at 38 percent, with towns and rural areas at 32 percent. Amusement parks and scenic parks were in the single digits.
Three out of five holiday travelers who responded to Triple A's survey said they would be staying with friends or relatives.