The National Weather Service said an advancing cold front would collide with a weather disturbance that became a tropical depression in the Gulf of Mexico.
The National Hurricane Center said the storm’s centre was 515km (320 miles) south-southwest of Lake Charles, Louisiana. It had maximum sustained winds of 55kph (35mph).
Forecasters issued a tornado watch for southern Mississippi and southwestern Alabama, and a powerful storm prompted a tornado warning for Mobile. But heavy rains were the immediate threat.
Parts of coastal Louisiana could receive as much as 25cm (10 inches) of rain Friday and Saturday, forecasters said, and 10cm (four inches) was possible across a wide section of Mississippi.
Streets were flooding around New Orleans and metro Birmingham, where about 7.5cm (three inches) of rain fell Friday morning, and more rain was on the way.
With scores of high school football games already rescheduled because of the weather, the University of Alabama cancelled its homecoming pep rally, bonfire and parade because of the forecast.
Rainfall totals ranging from 2.5 to 10cm (one to four inches) were possible from Alabama to South Carolina, the weather service said. Hurricane forecasters said there was a slight chance of flash flooding from the Texas-Louisiana line into northeastern Alabama.
The depression was predicted to move northward quickly, with its centre over Michigan by Sunday morning.