Rescue workers continue to search the rubble for victims in Warrick and Vanderburgh counties but officials say the death toll could climb even further.
Hundreds of rescuers are setting up lighting so they can continue searching through the night.
Authorities in hard-hit Vanderburgh County in Indiana say an eight-year-old girl's been taken to hospital after being found alive in a pile of debris.
National Guard troops are expected to brought in to assist after a local state of emergency was declared.
The National Weather Service is reported to have issued warnings for the
area about 30 minutes before the tornado hit at 2 am local time, but many people were asleep.
Alarm sirens only sounded about 10 minutes before the twister hit.
The tornado has left a path of destruction 32 kilometres long. On average tornadoes are 90 to 180 metres wide but this twister was nearly half a kilometre across.
A trailer park in Evansville, Indiana in the tornado’s path was devastated, killing 15 and leaving the local hospital flooded with more than 100 patients.
Meterologists at the National Storm Prediction Centre say such a severe tornado is rare in the US Midwest during November.
Peak tornado season is generally from April through June, although Ohio was hit with a similarly deadly funnel cloud three years ago in November.
But the midwest death toll has already eclipsed the ten fatalities reported this year from tornadoes in Georgia, Arkansas, Wyoming, Wisconsin and Mississipi.
On average tornadoes kill about 70 people annually in the United
States.