The unprecedented five-day closure will force hundreds of thousands of commuters to find alternate ways across the bay, setting the stage for crowded roadways, and packed buses, trains and ferries.
The California Highway Patrol plans to begin blocking traffic on and off the bridge at about 7:30 p.m., rerouting motorists to other freeways, according to Officer Daniel Hill.
The closure of the bridge, which opened in 1936, is expected to have region-wide effects on traffic, as nearly 300,000 vehicles cross the span daily.
People planning trips throughout the region over the Labor Day weekend are urged to check for alternative routes and transportation methods, officials said.
KGO-TV, ABC7's sister station in San Francisco, has a wealth of resources for those who will be affected by the closure. Visit the page here.
The new bridge is slated to open sometime late Monday or early Tuesday morning, with the opening chain-cutting ceremony scheduled for 3 p.m. Labor Day.
When the new bridge opens, Caltrans will start tearing down the old cantilever span, which will have to be dismantled piece by piece to avoid a collapse.
This weekend's closure is the fourth time in seven years that officials have shut down the bridge during the Labor Day weekend, when traffic is significantly lighter.
It will be nearly 24 years since the 6.9-magnitude Loma Prieta earthquake permanently damaged the existing eastern span, setting off a public works project marked by numerous delays, political fights over its design and complex engineering hurdles.
Officials say people will notice the old Bay Bridge largely gone within nine months but that it will likely take another two years to bring the old bridge and foundation down to the mud line.
Some of the pieces will be kept for historic purposes but much of the concrete and steel will be recycled or sold for scrap.
If you have to drive during the shutdown, download ABC7's Waze traffic app to get around the gridlock.
The Associated Press and ABC7 News San Francisco contributed to this report.