The snow and ice warning comes into force late on Monday evening and will carry through into Tuesday afternoon.
It affects the Highlands, Grampian, Strathclyde, South West Scotland, Lothian and Borders, Central Tayside and Fife, as well as parts of England.
Forecasters say on high ground in Scotland and across the higher Pennine routes there may also see up to 3cm of snow in places over the weekend.
But the main hazards are more likely to come from ice when the rain falls on frozen ground.
Posting on their website, the Met Office wrote: “Away from the coasts, 1-3 cm of snow is possible with up to 5 cm above 200 metres. As skies clear from the west early on Tuesday morning, ice may develop across western Scotland and Northern Ireland.”