The missing tourist submersible with five people onboard including British billionaire Hamish Harding is believed to have been above its destination when communication was lost.
OceanGate Expeditions, which owns and operates the vessel, was taking five people, including company CEO Stockton Rush, French submersible pilot Paul-Henry Nargeolet and Harding, to the wreckage of the Titanic.
The trip, which is thought to cost £195,000 per head, launched at 4am on Sunday, but communications disappeared one hour and 45 minutes into the two-hour descent to the Titanic wreck site - which sits about 3,800m (12,500ft) below sea level at the bottom of the ocean around 370 miles off the coast of Newfoundland but in US waters.
It is thought that the last "ping" from the submersible to its mothership MV Polar Prince located them just above the shipwreck.
Lieutenant Commander Len Hickey said a Canadian Coast Guard vessel and military aircraft were assisting the search effort led by the US Coast Guard in Boston.
OceanGate Expeditions, the private company which organises deep-sea expeditions, had confirmed in a statement that it owns the missing submersible. The company's managing director Mark Butler said the crew set out on Friday.
He said: "Every attempt is being made for a rescue mission. There is still plenty of time to facilitate a rescue mission, there is equipment on board for survival in this event. We're all hoping and praying he comes back safe and sound."
The missing submarine was designed with a 96 hour "emergency capability", Rear Admiral John Mauger, who is leading the rescue mission, announced at a press conference this evening - meaning there should be enough oxygen in the vessel until midday on Thursday.
There are fears that the submersible, named Titan, could be stuck in the wreckage of the Titanic that it was diving to explore.
The expedition was OceanGate's third annual voyage to chronicle the deterioration of the iconic ocean liner that struck an iceberg and sank in 1912, killing all but about 700 of the roughly 2,200 passengers and crew.
Since the wreckage's discovery in 1985, it has been slowly succumbing to metal-eating bacteria, and some have predicted the ship could vanish in a matter of decades as holes yawn in the hull and sections disintegrate.
Unlike submarines that leave and return to port under their own power, submersibles require a ship to launch and recover them. OceanGate hired the Canadian vessel Polar Prince, a medium duty icebreaker that was formerly operated by the Canadian Coast Guard, to ferry dozens of people and the submersible craft to the Titanic wreck site.
David Concannon, an advisor to OceanGate Expeditions who was supposed to be on the dive but could not go due to another client matter, said officials are working to get a remotely operated vehicle that can reach a depth of 20,000ft to the site as soon as possible.