Government officials have stripped Endangered Species Act protection from the wild animals in most of the country, putting state leaders in charge of overseeing them.
It prompted an outcry from conservationists and scientists who say hunting the animals could drive them close to extinction again, nearly 50 years after their numbers fell perilously low.
The decision is the latest in a series of actions on the environment by Mr Trump’s administration designed to appeal to rural voters in the final days of the presidential contest, including steps to allow more mining in Minnesota and logging in Alaska.
Department of interior secretary David Bernhardt said the grey wolf had exceeded conservation goals and no longer met legal definitions of a threatened or endangered species.
Gray wolves roamed the entire continent until state-supported hunting, poisoning and trapping drove them to near-extinction.
In 1974, with only about 1,000 remaining, they were added to the endangered species list. Four years later, the classification was downgraded to threatened.
Now there are about 6,000 in the lower 48 states, and experts say numbers are still so depleted that thousands of acres of ancient habitat in Utah, Colorado and Maine are uninhabited by wolves.
The new move, by the US Fish and Wildlife Service, will affect populations mostly in three midwestern states - Michigan, Wisconsin and Minnesota. A final rule is expected to go into effect early next week as voters go to the polls.
“Wolves will be shot and killed because Donald Trump is desperate to gin up his voters in the Midwest,” said Brett Hartl, government affairs director at the Centre for Biological Diversity.
Acclaimed primatologist Jane Goodall said she was shocked and saddened, and appealed to people to object to the move because wolves play a vital role in ecosystems.
“Wolves have all the sentience and emotions and intelligence, perhaps more so than dogs,” she said. “How would you feel if your dog was caught in a leg hold trap? Suffering for hours of agony? How would you feel if your dog was shot so that his head could be mounted on somebody’s wall?”
She added: “When this delisting was proposed in 2013 1.5m people spoke out against it … so please speak out again.”
“Stripping protections for grey wolves is premature and reckless,” said Jamie Rappaport Clark, president of Defenders of Wildlife and a former director of the US Fish and Wildlife Service.
“Grey wolves occupy only a fraction of their former range and need continued federal protection to fully recover. We will be taking the US Fish and Wildlife Service to court to defend this iconic species.”
But Safari Club International, the hunting group, and the National Cattlemen’s Beef Association issued a joint statement welcoming the decision. Farmers say killing wolves will help protect their livestock.
Earlier this year, Mr Trump’s government gave the go-ahead to hunting on national reserves in Alaska, allowing hunters shoot swimming caribou from motorboats, set dogs on black bears and kill bear cubs and wolf pups in their dens.
Environmental groups said protections were still needed to shield small populations of wolves in west coast states, including California.