With the added traffic will come added delays, particularly around areas hit hard by Hurricane Sandy.
"Holiday travel to those regions will most likely be more difficult than in previous years," said Brent Hubele, vice president of The Auto Club Group.
The bottom line: No matter where you're going, allow for extra time. In particular, here's a look at five roads to avoid, if at all possible, this Thanksgiving weekend:
1. Goethals Bridge area, Staten Island, N.Y.
In the wake of Hurricane Sandy, more motorists than usual have used the Goethals Bridge, which connects Elizabeth, N.J. with Staten Island, N.Y., as they contend with temporary living situations and emergency crews serve the area.
If possible, experts recommend avoiding the entire I-278 area and instead using the Bayonne Bridge to enter Staten Island. An added complication: New Yorkers currently face the highest gas prices in the nation, at $3.93 per gallon.
2. Los Angeles. All of it.
Admittedly, it may be difficult to avoid an entire city, but do so, if possible. Real-time traffic information provider Inrix projects that Los Angeles will have the worst traffic of any city this holiday season, with a 33 percent increase in traffic compared to a typical weekday.
Want one area to avoid in particular? A three-mile stretch of the Santa Monica Freeway surrounding the Interstate 405 area is expected to draw the heaviest traffic.
3. Dallas-Fort Worth Loop, particularly I-820 westbound.
Construction has slowed traffic to a crawl along the route that skirts north of Fort Worth toward Dallas. Thanksgiving traffic could double the time drivers need to drive from one city to another, according to researchers at the Texas A&M Transportation Institute.
Allow particular time if you have a flight to catch at DFW. Construction in Grapevine has turned all routes around the airport into a heinous jam.
4. San Francisco.
It's not so much a particular road to avoid around San Francisco, but particular times of day. The city has the second-busiest Thanksgiving rush-hour commute in the country, behind only Los Angeles, according to Inrix.
The real-time traffic provider advises that motorists either leave the city before 2 p.m. today, or wait until after 6 p.m. Likewise, AAA is advising drivers in the Bay Area to avoid driving between 3 p.m. and 7 p.m. if at all possible.
Both project that it will be more difficult to leave the city than enter.
5. Houston, Interstate 45 southbound.
On an annual basis, researchers say that commuters in the vicinity of the Sam Houston Tollway waste $4,557 sitting in traffic in this area of the interstate. It's going to be worse than usual throughout this weekend.
"There are a lot of shopping centers along this route and other activity centers along that area that people want to get to," Texas Transportation Institute researcher Bill Eisele tells Weather.com.