Flooding is possible on Saturday for large swaths of the country -- including hard-hit eastern Kentucky -- as millions of Americans are also under heat advisories.
Flash flooding is possible in the Ohio River Valley, as some parts may see 2 to 4 inches of rain.
Areas from Knoxville, Tennessee, to Pittsburgh, including nearly the entire state of West Virginia, have the greatest chances for flooding on Saturday, where slow-moving heavy downpours are expected.
That also includes eastern Kentucky, which was the site of devastating floods in late July. At least 37 people have been confirmed dead in the catastrophic flooding. Parts of the region were also hit with heavy rainfall on Friday. By midday Saturday, the heaviest rain had so far stayed clear of the worst-hit areas in last week's flooding. The flash flood threat is expected to subside in this region on Sunday.
In the Upper Mississippi Valley, areas between Minneapolis and Dubuque, Iowa, may also see flooding rains on Saturday, with 3 to 5 inches possible.
Saturday storms are expected to cause flight disruptions from New York to Florida and parts of Texas, Denver and Washington state, the Federal Aviation Administration warned. That comes after severe weather Friday night forced airlines to cancel more than 1,200 flights.
Meanwhile, more than 70 million Americans are under heat alerts this weekend, with heat alerts issued from Oklahoma to Maine.
In the Northeast, heat advisories extend from Delaware to Maine. Temperatures will feel like the mid-upper 90s for much of the Northeast coast Saturday.
Excessive heat warnings are in effect for Lincoln and Omaha, Nebraska, where the heat index is expected to surpass 110 degrees on Saturday.
Triple-digit temperatures are also forecast from Texas to Iowa.
The scorching temperatures are expected to persist in many of the same areas on Sunday.
ABC News' Dan Peck contributed to this report.