The storm's sluggish speed, roughly 5mph (7km/h), increases its capacity for destruction, pummelling coastal states with heavy rain.
The National Hurricane Center (NHC) reported flooding from Tallahassee, Florida to Mobile Bay in Alabama.
It also warned of a "life-threatening" storm surge and river flooding inland as far as Georgia.
Hurricane Sally is one of several storms in the Atlantic Ocean, with officials running out of letters to name the hurricanes as they near the end of their annual alphabetic list.
Alabama, Florida and Mississippi have all declared states of emergency. Louisiana Governor John Bel Edwards, whose state is still recovering from Hurricane Laura last month, tweeted on Tuesday that resident should all have a "game plan in place for whatever the rest of hurricane season has in store".
White House press secretary Kayleigh McEnany said on Wednesday that the administration is "fully engaged" as the storm continues to batter the Gulf Coast.
"It's safe to say the White House has been in active contact with all of these governors," she said on Fox News.