Motorists and rail passengers face severe travel disruption after roads became inundated and train services were cancelled - conditions made worse by road closures in place ahead of the United Nations climate change meeting.
Passengers travelling between Edinburgh and Glasgow are being advised to travel only if the journey is “absolutely necessary”, while Network Rail Scotland has imposed a speed limit of just 5mph on Glasgow-bound trains.
Network Rail said speed limits and reduced services would be in place on some routes between Wednesday and Friday, with disruption to the West Coast Mainline.
ScotRail said on Thursday there is disruption on "many routes this morning due to extremely heavy rain".
The first night of GlasGLOW, one of the city's biggest Halloween events, was abandoned on Wednesday evening just hours before doors were set to open, after "road-side drains were overwhelmed, flooding the road and entrance."
Traffic Scotland also reported flooding on the M74/A74(M) around Abington in South Lanarkshire, while just before 7am the entry slip at J13 was blocked due to a car stuck in water.
Several weeks' worth of rain is expected to fall in less than three days in parts of south-west Scotland.
A total of 12 flood warnings are also in place in the Scottish Borders where the council is advising people in Hawick living in at-risk areas near the river to “consider plans for evacuating their homes”.
Many parts of Cumbria have been hard-hit by heavy downpours and inundated roads, while the Met Office has warned of life-threatening flooding.
Up to 300mm of rainfall is expected in parts of the region. The average for October is 160mm.
South Lakes Police said the A591 road between Rydal and Grasmere is completely blocked off "due to the depth of flood waters" and urged people not to take unnecessary risks and only to travel if they really need to.
The Environment Agency in Cumbria said the Central Lake District has seen more than 12 inches of rain over the last 24 hours and "urged people to be prepared and ready to act".
The Scottish Environmental Protection Agency has issued 17 flood warnings and five flood alerts mainly covering southern Scotland.
The Met Office said there could be a “danger to life from fast-flowing or deep floodwater”.
The amber alerts also warn of potential damage to homes and businesses from flooding, dangerous driving conditions and travel disruption.
Communities could be cut off by flooded roads and face power cuts, according to the service.
“These are exceptional rainfall totals for even the wettest part of the UK, which is Cumbria on average, and for the wettest part of the year,” Met Office meteorologist Aidan McGivern said in a forecast video.
Liam Sumpter, Network Rail Scotland route director, said: “Extreme rainfall can pose a serious risk to the railway, causing landslips or damaging our infrastructure and bridges.
“The safety of our passengers and colleagues is our main priority during periods of poor weather, and slowing services down and running fewer trains will help us manage these conditions for everyone.”
On Thursday, south-west England and Wales are forecast to be hit, with a yellow weather warning for rain across much of Wales until Friday afternoon.
Some disruption is expected, particularly in the Brecon Beacons and Snowdonia, though not as widespread or impactful as other affected areas of the UK, according to the Met Office.