The US Coast Guard said one pilot and four passengers were on board and the vessel had the capacity to be submerged for 96 hours but it was unclear whether it was still underwater or had surfaced and was unable to communicate.
British billionaire Hamish Harding is among the passengers, according to a social media post from a relative.
US and Canadian ships and planes have swarmed the area about 1450 kilometres east of Cape Cod, some dropping sonar buoys that can monitor to a depth of 3962 metres, US Coast Guard Rear Admiral John Mauger told reporters on Monday.
"It is a remote area and it is a challenge to conduct a search in that remote area," Mauger said.
"We are deploying all available assets to make sure that we can locate the craft and rescue the people on board," he said.
"Going into this evening we will continue to fly aircraft and move additional vessels."
Mauger said officials have also been reaching out to commercial vessels for help.
The private company that operates the submarine, OceanGate Expeditions, said in a statement on Monday it was "mobilising all options" to rescue those on board.
The US Coast Guard said earlier on Twitter a boat on the surface - the Polar Prince - lost contact with the submarine, called the Titan, about one hour and 45 minutes after it began diving toward the site of the Titanic's wreckage on Sunday morning.
"We are deeply thankful for the extensive assistance we have received from several government agencies and deep sea companies in our efforts to re-establish contact with the submersible," OceanGate said.
Harding's stepson wrote on Facebook that Harding had "gone missing on submarine" and asked for "thoughts and prayers".
The stepson subsequently removed the post, citing respect for the family's privacy.
Harding himself had posted on Facebook that he would be aboard the sub.
There have been no further posts from him.
The expedition headed out to sea on Friday, and the first dive was set for Sunday morning, according to Harding's post.
The expeditions, which cost $250,000 per person, start in St John's, Newfoundland, before heading out approximately 640km into the Atlantic to the wreckage site, according to OceanGate's website.
To visit the wreck, passengers climb inside Titan, the five-person submersible, which takes two hours to descend approximately 3800m to the Titanic.
Harding is a holder of three Guinness World Records: longest duration at full ocean depth by a crewed vessel, longest distance traversed at full ocean depth by a crewed vessel and fastest circumnavigation via both poles by aeroplane.
Two of these feats were achieved by Harding and ocean explorer Victor Vescovo when they dived to the lowest depth of the Mariana Trench - the deepest part of the ocean - in a two-person deep-submergence vehicle in March 2021.
The Titanic passenger ship famously sank in 1912 on its maiden voyage after striking an iceberg, killing more than 1500 people.
