An Amazon Air cargo plane overshot the runway while attempting to land at Miami International Airport, killing five people and seriously injuring five more.
The Boeing 767-300 cargo aircraft crashed just before 14:00 local time (19:00 GMT) after departing from Luis Muñoz Marín International Airport in San Juan, Puerto Rico. The flight also hit several vehicles on the ground.
Amazon said that it is "working closely with local authorities and officials to understand exactly what happened".
All flights were ordered grounded by the Federal Aviation Administration (FAA) as fire crews raced to the smoking crash site. The crash comes over Labor Day weekend, one of the busiest travel times of the year.
"At least five people have lost their lives, and five others are injured," Miami-Dade County Mayor Daniella Levine Cava said at a news conference on Sunday evening.
She added that rescue crews arrived at the scene within "seconds" of the crash.
"Right now, our focus is on the families, those who were injured, and the ongoing response," she continued.
Three of the five people injured are in critical condition, said Miami Fire Chief Raied Jadallah. The mayor said they were all taken to hospital with "unknown injuries".
Several of the injured were trapped inside or under vehicles on the ground, and needed to be extricated by fire and rescue crews, said Jadallah.
Officials say it is too early to know the cause of the crash, and that it will be investigated by the National Transportation Safety Board. The federal agency, which investigates all air crashes in the US, plans to hold a news conference on Monday.
The Amazon flight operated by 21 Air, a charter company based in North Carolina, "overran Miami International Airport's diagonal runway and is disabled at the northwest end of the airport," the airport said in a statement.
Miami Dade Fire Rescue said crews "arrived to find an airplane that had caught on fire as a result of this crash, with heavy flames and smoke showing".
Over 200 firefighters responded to the crash. The flames were extinguished, but there is still a fuel leak at the site, said Jadallah.
Amazon issued a statement saying that it is working closely with authorities and offering condolences to the victims.
"We're heartbroken to learn that five people lost their lives in today's incident at Miami International Airport," said Kelly Nantel, Amazon's Director of Corporate Global Media Relations.
"Our deepest sympathies go out to the families, loved ones, and all those affected by this devastating loss.
"The airplane, which was operated by 21 Air, was attempting to land when this incident occurred. We're working closely with local authorities and officials to learn more and will cooperate fully with any investigation."
The BBC has emailed 21 Air about the incident, but has not received a response.
Flight data from tracking site FlightRadar24 shows that the Amazon cargo flight was travelling at 112 knots (129mph, 207km/h) as it exited the "useable runway".
In a blog post, the site says the plane came to rest near a parking lot that services an Amazon warehouse and other businesses.
There were light thunderstorms and gusting winds in Miami at the time of the incident, the site says.
The crash comes during one of the busiest travel weekends of the year in the US.
Passengers at Miami International Airport airport told the BBC they were frustrated by the lack of information coming from officials, with many flights cancelled or delayed as a result of the incident.
There were long lines at airline counters as people tried to reschedule travel plans, with some saying they would be forced to stay in Miami an extra night.
The Transportation Safety Administration (TSA) said there would be 17 million travellers passing through US airports in the week leading up to Monday's Labor Day holiday.
The TSA, which screens passengers flying in the US, predicted that 2.3 million people would fly on Sunday alone.
Miami International Airport (MIA) is located near downtown Miami, and is one of the busiest airports in the country.
"Founded in 1928, MIA is America's busiest airport for international freight and second busiest for international passengers, offers more flights to Latin America and the Caribbean than any other US airport," according to their website.
About 60% of all international visitors to Florida arrive at this airport, it says.
