More than 200 motorists were stranded overnight on the M74 as heavy snow and ice caused treacherous driving conditions.
Dozens of schools have been closed in some parts of Scotland, while public transport has been disrupted by the weather.
Police Scotland closed parts of the motorway in Lanarkshire in both directions due to wintry conditions for a number of hours overnight – with tailbacks stretching 12 miles southbound and seven miles northbound at one stage.
Mountain rescue teams were drafted in to check on drivers, many of whom were stuck in their vehicles for several hours after heavy snow showers hit the area throughout Tuesday evening and into the early hours of Wednesday.
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Police declared a critical incident as they dealt with the situation and said that more than 200 people were stranded.
Transport Scotland said the M74 was now open in both directions, but that conditions remain challenging after a “very difficult night”.
Agencies are now working to keep the traffic moving.
Chief Superintendent Stewart Carle told BBC Good Morning Scotland: “The gritters are out, they are continually putting down more grit and ploughing, they are using heavy rescue vehicles to give jack-knifed lorries a tow to get them straightened up again, this will be a slow process and if the weather looks like it’s going to turn again please listen in, we may give a message to say avoid travel on the M74.”
Moffat Mountain Rescue assisted the operation to get the road clear by walking on the motorway and visiting drivers stuck in the tailbacks.
All schools in the Borders are closed due to the weather while 16 secondary schools, 58 primaries and 44 nurseries in the Highlands are shut.
Around 20 schools in Dumfries and Galloway and 28 schools and nurseries in South Lanarkshire are also closed.
The Met Office has issued yellow “be aware” warnings of snow and ice for much of the country which are valid until Friday.
More than a foot (36cm) of snow was recorded in Eskdalemuir in Dumfries and Galloway, Glenanne in Co Armagh had 23cm, while Tulloch Bridge in Inverness saw 21cm of snow overnight with temperatures as low as minus 4C, forecasters said.
Elsewhere across England and Wales, the mercury did not reach above 2C.
Meteorologist Alex Burkill said: “There have been plenty of heavy snow showers, particularly across Scotland. It’s pretty bleak out there in some places. A good chunk of the UK is effectively covered by snow and ice warning this morning.”
Looking ahead for Wednesday, he added: “It is going to be quite windy as low pressure pushes through tonight and that could bring some snow across parts of Scotland and in particular northern England.”
Forecasters warned the winds could reach 70mph across northern England and Wales on Wednesday evening – and potentially could be another named storm.
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Mr Burkill added: “Once that clears out, we will return to frequent showers pushing in from the north west through Thursday and Friday.”
Police Scotland warned there is a high risk of disruption for journeys and said drivers of HGVs should drive with extreme caution.
“Winter driving is a question of common sense and drivers should ask themselves if they really need to travel when conditions are poor,” police said in a statement.
“If you are travelling on the roads, you should ensure you and your vehicle are adequately prepared for the conditions, making sure you have sufficient fuel and supplies such as warm clothing, food and water in the event you are delayed for several hours,” officers added.