A UPS aircraft crashed after departing the Louisville Muhammad Ali International Airport in Kentucky, federal authorities said Tuesday, sending a massive plume of smoke into the air and leading authorities to urge residents of a large swath of the nearby area to shelter in place following the fiery crash.

There are reported injuries, according to the Louisville Metro Police Department, which did not specify how many.

Three crew members were on board the plane, according to UPS, which said it has not confirmed any injuries.

A shelter-in-place was initially issued within 5 miles of the airport but was subsequently expanded to all areas north of the airport to the Ohio River, police said.

“This is an active scene with fire and debris. Stay away,” the Louisville Metro Police Department said on social media.

Louisville Mayor Craig Greenberg said the city has “every emergency agency responding to the scene.”

“There are multiple injuries and the fire is still burning,” he said on social media. “There are many road closures in the area — please avoid the scene.”

UPS Flight 2976 crashed around 5:15 p.m. local time on Tuesday, according to the Federal Aviation Administration. The McDonnell Douglas MD-11 was headed to Daniel K. Inouye International Airport in Honolulu, the agency said.

It appears there was an engine issue during takeoff, sources told ABC News.

UPS said it has been “notified of an incident/accident involving one of our aircraft” in Louisville.

The airport is home to UPS Worldport, the company’s massive package handling facility.

The FAA and the National Transportation Safety Board are investigating the crash.

The airport confirmed there was an “aircraft incident” and that the airfield is closed.

“Kentucky, we are aware of a reported plane crash near Louisville International Airport,” Kentucky Gov. Andy Beshear said 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.”

Beshear said Tuesday evening that he is en route to Louisville.

“The situation is serious. Please pray for the families affected,” he said.

ABC News’ Luke Barr, Sam Sweeney and Ayesha Ali contributed to this report.

This is a developing story. Please check back for updates.