There are two-mile queues on the motorway and congestion along the diversion route.
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Drivers on the M25 in Surrey are facing miles of tailbacks after “unprecedented” closures came into force.
A five-mile stretch along both carriageways between junctions 10 and 11 was closed at 21:00 GMT Friday and will remain shut until 06:00 on Monday.
There is congestion on the detour route, with drivers told not to “try to be clever” and seek out alternatives.
People should only use the M25 if “absolutely necessary”.
The M25 is also being held clockwise between junction five, near Sevenoaks, and junction six following a multi-vehicle crash.
“Delays are building on the approach,” National Highways said.
Traffic has been flowing fairly steadily along the designated detour route, but Surrey Highways warned it was building between Byfleet and Painshill, with two miles of congestion on the approach to the closure.
It is the first time there has been a scheduled daytime closure of all lanes on the M25 since it opened in 1986.
It is to enable the demolition of a bridge and the installation of a new gantry, which is now in place.
The closure is part of the junction 10 improvement scheme, which is due to be completed in mid-2025.
National Highways said the carriageway between junctions nine and 11 typically carried between 4,000 and 6,000 vehicles per hour in each direction between 10:00 and 21:00 at the weekend.
The Sun is reporting that Tom Cruise has helicopters on standby ready to fly the cast and crew of the latest Mission Impossible film to Surrey’s Longcross Studios if they cannot get there because of the closures.
Cruise’s representatives have not responded to an approach from the BBC, while Longcross Studios declined to comment.
The village of Byfleet is on the detour route and residents headed to a motorway bridge to photograph the empty lanes.
Councillor Amanda Boote described it as a “moment in history”.
She added: “The traffic is starting to build up now but it was lovely overnight.
“We could hear the birds singing and we all slept well.”
Mark Pollak, owner of caterers Billy Tong, said he expected to see 50% of the firm’s weekend turnover go “down the drain”.
He said he had to refuse a request to cater an event in Guildford and was forced to cancel its stall at a market.
Cobham Veterinary Centre is also on the diversion and has been affected by roadworks for more than a year.
Andrew Bradnock from the vets told BBC Breakfast: “We’ve had a few clients who have now left because getting backwards and forwards to us is so difficult for them they decided to move to practices closer to them.
“There’s no way I’m going be able to get in or out of here, it’ll be gridlock because the diversion they have set is virtually going past our front door.”
Image source, Getty Images
Emergency services are also warning of a difficult weekend.
South East Coast Ambulance Service said on X, formerly Twitter: “It’s likely to be a challenging weekend for our teams.
“Please be aware of any emergency vehicles looking to progress through any likely heavy traffic.”
St Peter’s Hospital in Chertsey, Surrey, warned people to “only visit if necessary”.
Travellers affected may include people going to Gatwick and Heathrow Airports and the Channel ports, as well as concert-goers, sports fans and holidaymakers travelling to London and surrounding areas, National Highways said.
Steve Gooding, director of the RAC Foundation, told BBC Radio 4 Today programme if people needed to catch a flight they should take the train or allow plenty of time if they drive.
“It is unprecedented. We haven’t closed the M25 for an entire weekend before… so the best thing is allow plenty of time and think ahead,” he said.
The closure will be the first of five between now and September as part of a £317m upgrade, with the next due in April.
National Highways previously said it was not yet at a stage where it could release exact dates about the other closures.
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