As Isaac moved northward through Louisiana, the storm was spinning off tornadoes across Mississippi and Alabama, and leaving torrential rains and massive flooding in its wake.
The Department of Energy said at 6 p.m. ET that Alabama, Arkansas, Louisiana and Mississippi have reported a total of 1,000,457 customers without power.
Isaac caused its first death in Pearl River County, Miss., early today when a male tow truck driver was killed on the job by a tree that fell around midnight, Pearl River Emergency Management Deputy Director Amanda Harris told ABC News. The man's name and age were not immediately released.
"[The county] is completely flooded. And it's only going to get worse," Harris said, adding that rivers and creeks along the county along the Louisiana border will not crest until midnight through 4 a.m. Friday.
"The worst is yet to come," Harris said.
Pearl River County conducted four search-and-rescue operations and it was believed there were no more residents in their homes, Harris said. The county was receiving assistance from FEMA, state agencies and neighboring counties.
Lt. Vernon Smith of the Pascagoula, Miss., police told ABC News that a tornado touched down at approximately 8:20 a.m. just south of Pascagoula, which is located 28 miles from Biloxi.
"It landed right on top of a house, just sat on it," Smith said, adding that people were believed to be inside. "There are people injured."
Smith said the tornado then lifted off the ground and moved through the main part of town, having traveled about a mile since touchdown. Officials are mobilizing emergency crews, but the torrential rain made roads impassable, with the 2 to 3 feet of water flooding the area too much for even their emergency vehicles to handle.
"We can't get through and we are scrambling," said Smith.
Surrounding areas of Louisiana were expected to see almost two feet of rain and more dangerous floods by the end of the week, while seven tornadoes had spun off from Isaac in Mississippi and Alabama.
A tornado that touched down in Gulfport, Miss., caused significant destruction reported to homes. Carlos Redmond, a spokesman for Harrison County Emergency Management, said it was assessing the damage.
"We're looking for daylight. That's what we're looking for. We'll be able to tell a lot more at that time," Redmond told ABC News Thursday.
The rising waters from rain and flooding left locals scrambling up to attics and onto roofs. The main parishes that pose the greatest concern sat around Lake Pontchartrain. With another 4 to 7 inches of rain expected, many officials have expressed worry about the rising waters.
Officials in LaPlace, La., about 25 miles northwest of New Orleans, in St. John the Baptist Parish, called the situation dire.
"I'm afraid the tide is really going to catch some of us off guard tonight," Parish President Layton Ricks told ABC News late Wednesday night.
Livingston Parish officials told ABC News that they felt the worst of Isaac at 10 p.m. Wednesday, and expect flooding in the low-lying parts of the parish. Rescue efforts were under way and officials said this will be the first overnight of many water rescues in the area.
More than 725,000 homes and businesses throughout Louisiana were without power as of 2 a.m. Police reported few problems with looting.
President Obama declared federal emergencies in Louisiana and Mississippi late Wednesday, according to a statement from the White House. The disaster declarations free up federal aid for affected areas.
ABC News' Max Golembo and The Associated Press contributed to this report.