The bridge has been closed three times over Labor Day weekend since 2006, and has never caused traffic jams. But this year, the closure begins 8 p.m. Wednesday and lasts until 5 a.m. Tuesday -- two days longer than in past years.
This is the first time it has included weekdays, when thousands of drivers are commuting to work or preparing to leave town for the long weekend.
AAA predicts a 6 percent increase in the number of cars on state roads this weekend compared to 2012 -- more than 3.9 million Californians will travel more than 50 miles from their homes.
San Francisco officials have recommended drivers add one to two hours to their driving time to the city while the bridge is closed.
"Taking the Bay Bridge out of the equation is mind-boggling," said Bay Area traffic reporter Joe McConnell. "It could be chaos those two afternoons."