The heatwave could affect about 200 million people in major cities like New York, Washington and Boston in the East Coast, and the Midwest region too.
In some places, temperatures could be close to or exceed 100F (38C).
Experts say heatwaves are becoming more frequent, a phenomenon that is linked to climate change.
The world experienced its hottest June on record this year, with an average temperature worldwide of 61.6F (16.4C), according to new data.
Earlier this month, the US state of Alaska, part of which lies inside the Arctic Circle, registered record high temperatures.
Which areas are hit by the latest heatwave?
The heatwave is hitting an area stretching from the Central Plains of Colorado and Kansas, to the Great Lakes in the north-east.
Temperatures are also rising in most areas of the East Coast.
The National Weather Service (NWS) published a map of the areas that are affected.
“The hazy, hot and humid conditions will persist through the weekend. Be smart and stay cool!” it warned.
New York Mayor Bill de Blasio declared “a local emergency due to the extreme heat” in the city.
“This is a heatwave coming up these next days. It’s serious stuff,” the mayor said in a video posted on Twitter.
“Friday is going to be bad. Saturday is going to be really, really bad on through Sunday.”
He urged New Yorkers to take the threat seriously, to stay hydrated, and to not go out in the hot weather.
Mr de Blasio added that 500 “cooling centres” were being opened across New York.
Similar measures were being taken in Detroit and other cities.
What is the forecast?
US meteorologists say the heatwave is expected to continue through the weekend, and some cities may see their highest temperatures in years.
In some cities it might feel as hot as in California’s Death Valley – a desert region known for its extreme heat.
Humidity will make it feel a lot hotter than the listed temperature in some places, meteorologists warn.
But they say a dramatic change is on the way early next week, when it is expected to suddenly cool off.