A "heat-dome" settling over western Europe could bring temperatures of up to 40C in some parts of England and Wales in the middle part of the week, the Met Office said.
Temperatures for the latest heatwave are likely to overtake the June record set in Hampshire in 1976 by several degrees and could come close to the UK's all-time high of 40.3C in July 2022.
The hot conditions, which have been very rare in the UK until now, will be accompanied by high humidity and very warm nights, which will make it hard for people to recover overnight, the forecaster warned.
A red weather warning for extreme heat covering an area stretching from London to Swansea and Somerset to Birmingham was issued by the Met Office from 9am on Wednesday to 9pm on Thursday.
The Met Office said the heatwave is expected to bring "severe and significant impacts" including widespread health risks for many, not just those who are normally more vulnerable to the heat, and even endanger lives.
Scores of schools across England and Wales announced they would close or finish early to protect pupils amid the extreme heat.
The Buckingham School in Buckinghamshire said it would be closed on Wednesday and Thursday.
"Because most of our buildings cannot be cooled adequately and there is little shade outside, we have taken the difficult decision to close the school site on both days (Wednesday and Thursday), a statement on its website said.
Advice has also been issued for transport users, with Network Rail warning passengers should "only travel if absolutely essential on Wednesday and Thursday".
"Extreme heat can have a significant impact on the railway, so safety must come first," deputy chief executive of Network Rail Jake Kelly said.
"We're asking passengers to check before travelling on Tuesday, and only travel if absolutely essential on Wednesday and Thursday if they are going to, from or within the red warning zone as temperatures are expected to peak."
The UK Health Security Agency issued a red health warning for six regions of England - the West Midlands, East Midlands, South East, South West, London, and east of England - from 1am on Wednesday until 11pm on Thursday.
This indicates "a risk to life for even the healthy population" as well as impacts beyond health and social care, with potential effects on transport systems, food, water, energy supplies and businesses.
Transport for London warned customers of possible disruption to rail and Tube services, saying rail temperatures could lead to temporary speed restrictions and reduced services.
"Customers should be aware that, given the very high temperatures that are forecast, we are likely to see some disruption to rail and Tube services – with rail temperatures likely to lead to temporary speed restrictions and therefore reduced services in some cases," TfL's chief operating officer Claire Mann said.
