The US President's warning comes just days after it was revealed that Trump was preparing to deploy attack drones into North Korea to take out Kim Jong-un.
The companies and vessels are from throughout the world, including North Korea, China, Singapore, Taiwan, Hong Kong, Marshal Islands, Tanzania and Panama.
The restrictions were made against 50 vessels, shipping companies and trade businesses.
"We imposed today the heaviest sanctions ever imposed on a country before", Trump said.
Mnuchin said the actions will significantly hinder North Korea's ability to conduct evasive maritime activities that facilitate illicit coal and fuel transports, and "erode its abilities to ship goods through global waters".
Remarks from the South Korean side have come at a time it has emerged the reclusive Kim-regime had cancelled possible high-ranking talks with the United States at the last-minute.
U.S. Vice President Mike Pence had hinted at such a sanctions package two weeks ago during a stop in Tokyo that preceded his visit to South Korea for the Pyeongchang Olympics.
"We are working on Russian Federation sanctions", Mnuchin said.
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"But hopefully the sanctions will work", Trump added.
It defends the weapons programs as essential to deter USA aggression.
North Korea on Thursday accused United Nations Secretary-General António Guterres of "picking a quarrel" with Pyongyang by praising worldwide sanctions for putting pressure on the country over its nuclear and ballistic missile programs.
The U.N. Security Council's 15-member sanctions committee operates by consensus behind closed doors.
The Japanese Ministry of Foreign Affairs has released imagery of another suspected ship-to-ship fuel transfer between a North Korean product tanker and a Chinese-controlled vessel. However, Mnuchin didn't rule that out.
However, United Nations measures in recent months have ramped up economic pressure and made it more hard for North Korea to import oil and other essential products. Senior administration officials noted on Friday that the president is frustrated with "upticks" he has seen in North Korea's nuclear program and is prepared to do whatever he can to target the various ways the regime is able to generate money.
The North Korean regime is facing unprecedented levels of pressure.
"President Moon also said out of all countries, South Korea has the strongest will to say it can not acknowledge North Korea as a nuclear state", he said. "We know they continue to undermine our efforts to isolate North Korea".
In light of this concern, the United States will send out a shipping advisory highlighting the warning signs that other nations need to watch for, a senior White House official.