The Met Office has issued amber "be prepared" warnings for snow in the Highlands, Central, Tayside, Fife, Strathclyde and Grampian from 3am until 11am, and yellow "be aware" alerts for snow in Orkney, Shetland and Lothian and Borders.
Transport Minister Keith Brown said tomorrow morning could present the biggest winter challenge so far.
Sleet and snow are forecast to spread after a cold night with widespread frost, with 10-15cm of snow likely on levels above 400m and 5-10 cm expected on areas above 200m.
Mr Brown said the multi-agency response team will monitor the morning rush-hour travel and offer help.
"So far this week the network and the public have coped well with some testing conditions. However, this severe weather warning suggests that tomorrow morning promises to be the biggest challenge of the winter to date.
"We would remind motorists and the travelling public to be aware of the potential dangers of snow and icy conditions. An added risk is that fresh snow could fall on hard-packed ice and already-treacherous surfaces, so keep up to date with live travel information and advice for preparing for and driving in testing conditions.
"The public should be prepared for the risk of significant disruption to travel, especially over the M8 corridor to the east of Glasgow, across Perthshire and over much of inland eastern Scotland."
David Simpson, route managing director of Network Rail Scotland, said: "We're monitoring the weather forecast and deploying our rapid response teams to where the weather is most likely to hit.
"In the past couple of years we've invested heavily in innovative technology such as Nasa-grade insulation to prevent points freezing and snow displacers which prevent snow building up. This will make the network as robust as possible and help us to keep Scotland moving."
Anthony Astbury, chief forecaster at the Met Office, said temperatures could drop to minus 60C widely and to even lower in more rural locations.
"At lower levels, 2-3cm of snow is likely before turning back to rain. Despite turning to rain, the lying snow and ice will struggle to melt and this will bring some treacherous conditions," he said.