Early flight data indicated the 27-year-old converted freighter operated by K2 Airways possibly crashed into the sea southwest of Karachi after a series of sharp altitude changes before a steep final descent, according to flight-tracking service Flightradar24.
Authorities have launched a co-ordinated search and rescue operation at sea through various agencies to locate the missing plane, Pakistan Airports Authority said on Facebook.
The plane reported a navigational system issue at 9:18pm on Tuesday (2:18am Wednesday AEST) while flying toward Karachi, the airports authority said.
Local air traffic control tried to guide the aircraft, but three minutes later radar systems showed the plane descending rapidly and communication was lost, the authority said. The flight was about 155 nautical miles west of Karachi at the time.
The aircraft went missing while flying over the Arabian Sea near Ormara in Balochistan, Pakistan, local media Geo News reported.
Flightradar24 said data showed the aircraft first lost altitude, then briefly climbed, before a second, sudden and dramatic drop.
It added that the last transmitted data point placed the aircraft at 1,100 feet above sea level, with a vertical rate of minus 22,400 feet per minute, an extremely steep and abnormal rate of descent.
The missing aircraft is part of Boeing's decades-old 737 family but is two generations older than the 737 MAX version that was involved in a recent safety crisis. It uses engines made by CFM International, jointly owned by GE Aerospace and France's Safran.
The 737-400 was first delivered as a passenger plane to Russia's Aeroflot in 1999 and was converted to a freighter in 2012, according to Flightradar24.
It is K2 Airways' only aircraft and entered into service with the carrier in 2024.
K2 Airways and Boeing did not immediately respond to requests for comment.
If casualties are confirmed, the incident would be the first fatal crash in Pakistan since 2020, when a Pakistan International Airlines Airbus A320 came down short of the runway in Karachi, killing 97 people after pilots were distracted discussing the coronavirus before a failed landing attempt.
