The M25 is now closed in both directions between junctions 9 and 10 in Surrey amid warnings of delays and a 19-mile diversion.
The road closed at 9pm on Friday and will remain shut until 6am on Monday morning while concrete beams for a new bridge are installed.
National Highways senior project manager Jonathan Wade told drivers to leave extra time, follow official diversion routes and to “only travel if absolutely necessary”.
Diversion routes will take cars on a 19-mile journey on A roads, crossing from Surrey into London’s Ulez area, though National Highways has assured drivers “no enforcement action will be taken”.
The closure comes weeks after the motorway’s first-ever planned daytime closure over the weekend of March 15 which saw two-mile tailbacks.
Many drivers heeded advice to avoid the area in March allowing, meaning long traffic james to be avoided but Mr Wade warned this closure - which is two miles longer than the last - will be “far from a repeat of the previous closure”.