Watch: How to cope with extreme temperatures during the heatwave
The heatwave is likely to have "widespread impacts" across England, with hospitals and train services set to come under further stain.
The UK's temperature record is likely to be broken when the heatwave peaks on Tuesday, when highs of 40C (104F) are possible.
Here is everything you need to know about the weather alert.
What is a red weather warning?
The Met Office's historic red warning means the heatwave could lead to "serious illness or danger to life".
The alert, which is place for Monday and Tuesday, covers an area from London up to Manchester, and across to the Vale of York.
People have been urged to ensure "suitable measures" are in place to help vulnerable relatives or neighbours cope with the heat.
Forecasters gave an 80% chance of the mercury topping the UK's record temperature of 38.7C, and a 40% chance of it topping 40C.
Met Office chief meteorologist Paul Gundersen said: "Nights are also likely to be exceptionally warm, especially in urban areas.
"This is likely to lead to widespread impacts on people and infrastructure. Therefore, it is important people plan for the heat and consider changing their routines.
"This level of heat can have adverse health effects."
Met Office spokesman Grahame Madge added: "If the forecast is as we think it will be in the red warning area, then people's lives are at risk. This is a very serious situation."
Has a national emergency been declared?
The UK Health Security Agency (UKHSA) declared a national emergency by upgrading its heat health warning from level three to level four.
Level four is reached "when a heatwave is so severe and/or prolonged that its effects extend outside the health and social care system".
"At this level, illness and death may occur among the fit and healthy, and not just in high-risk groups," the UKHSA said.
Dr Agostinho Sousa, head of extreme events and health protection, said: "It is important to keep yourself hydrated and to find shade where possible when UV rays are strongest, between 11am and 3pm.
"If you have vulnerable family, friends and neighbours, make sure they are aware of how they can keep themselves protected from the warm weather."
Is climate change to blame?
Scientific studies have shown that climate change is making heatwaves longer, more extreme and more frequent.
The Met Office's Grahame Madge said: "If we get to 40C that's a very iconic threshold and shows that climate change is with us now.
"This is made much more likely because of climate change."
Mike Childs, head of science, policy and research at Friends of the Earth, said: "Each year, the effects of climate breakdown are becoming more evident and more severe.
"Without meaningful government intervention, millions of Brits, particularly older people and young children, will be at increasing risk from health-threatening heat waves like the one we’re experiencing."