The McDonnell Douglas MD-11 was headed to Daniel K. Inouye International Airport in Honolulu, FAA officials said. The aircraft was likely loaded with jet fuel at the time of the incident, leading to a massive fireball explosion.

The Louisville Metro Police Department confirmed its officers, along with multiple other agencies, were responding to the crash, which happened near the UPS Worldport.

Black smoke could be seen near the Louisville Muhammad Ali International Airport (SDF) in Kentucky. (Credit: X / @WT_Mason)

Police said multiple people were injured, though UPS wrote in a statement it has not confirmed any injuries or fatalities.

"This is an active scene with fire and debris," police wrote in an X post. "Stay away."

The agency later issued an emergency shelter-in-place alert for all areas north of the airport to the Ohio River.

The FAA and National Transportation Safety Board (NTSB) will investigate, with the NTSB taking the lead.

"Kentucky, we are aware of a reported plane crash near Louisville International Airport," Kentucky Gov. Andy Beshear wrote in a statement on social media. "First responders are onsite, and we will share more information as available. Please pray for the pilots, crew and everyone affected. We will share more soon."

He later added the situation is "serious," and said he was on his way to Louisville.

Anna McMullen, who lives seven minutes from the airport, told Fox News Digital her husband called her and thought "something was burning" downtown.

"All you could see in the sky around the airport was black smoke in billows," McMullen said. "I heard explosions, and they are still going off, which means the plane could have hit the petroleum supply tanks."

Louisville plane crash

A house near the location of a plane crash that took place in Louisville, Ky., on Tuesday afternoon. (WDRB)

She added that the normal pattern for the UPS planes is to be loaded before they take off. 

"We have lived here 25 years and have never seen a UPS plane crash," McMullen said. "The sun has set, but the smoke is still horrible. We can still hear the explosions."

Ford, which has an assembly plant nearby, confirmed to Fox News Digital that its facility was not affected, and that all personnel are safe.

In a statement on its website, UPS committed to releasing "more facts as they become available, but the National Transportation Safety Board is in charge of the investigation and will be the primary source of information about the official investigation."

UPS did not immediately respond to additional inquiries from FOX Business.