City officials announced the mid-July closure more than a month ahead of time to prepare for what some residents are calling "Carmageddon."
Interstate 405 connects to several other Los Angeles highways, including Interstate 5, the primary north-south West Coast link between the Mexican and Canadian borders.
The focus of the shutdown is planned demolition work on the Mulholland Bridge, part of a I-405 widening and improvement project. The shutdown is scheduled for Friday, July 15, with ramps closing as early as 7 p.m., freeway lanes starting to close at 10 p.m. and the highway fully closed by midnight.
The route will reopen at 5 a.m. on Monday, July 18.
The freeway will close between Interstate 10 and U.S. 101, also known as the Ventura Freeway.
On a typical weekend, an estimated 500,000 vehicles travel this stretch of road, according to the Los Angeles County Metropolitan Transportation Authority.
Significant delays are expected along I-10 and U.S. 101, the most direct path around the closure. Those who need to travel through the area during the closure should plan other alternative routes, Los Angeles officials said.
They have advised drivers to "plan ahead, avoid the area, or stay home," according to a joint press release by the Los Angeles Police Department, Fire Department, California Highway Patrol, Los Angeles Department of Transportation, Metro and California Department of Transportation.
The northbound side of I-405 will be closed for 10 miles and southbound for four miles for the demolition of the south half of Mulholland Bridge.
This is part of the I-405 Sepulveda Pass Improvements Project, which ultimately will widen the freeway and bridge and add a northbound high-occupancy vehicle lane.
Maps of the affected routes and a detailed closing schedule are on the Los Angeles County website at www.metro.net.
Caltrans and the Los Angeles County Metro are overseeing the Sepulveda Pass project, scheduled to finish in 2013.
Officials said side roads would not be viable alternatives during the shutdown.
"Sepulveda Boulevard will not have the capacity to accommodate both local and diverted traffic," Metro representatives said in a statement. "Motorists should instead use alternate regional freeway routes to completely bypass the Sepulveda Pass."
I-405 will be closed again next year to repeat the process on the north half of Mulholland Bridge.
Sections of I-10 (San Bernardino Freeway) also will close later this July to construct eastbound and westbound HOV lanes, according to a Caltrans statement.