The long-promised highway is expected to take four years to build, with construction happening only during the winter months when the ground is firm. Initial construction started early last year.
The federal government has promised $200 million for the highway, with the territory voting last spring to spend $65 million on it, in addition to $12 million already invested in getting the project started.
For years, people in the Northwest Territories' Mackenzie Delta region lobbied for the 140-kilometre all-weather road to link the two communities, which are currently connected by air or ice road only.
About 1,000 jobs will be created over the four-year construction period.
For the Conservative government, it will stretch Canada's road network further north and hearkens back to former prime minister John Diefenbaker's vision of connecting the north to the rest of Canada.
N.W.T. Premier Bob McLeod and federal Environment Minister Leona Aglukkaq will be at the ceremonial groundbreaking along with Harper.
The project has faced criticism, with some arguing the benefits are questionable.
MLA Norman Yakelaya argued in October that the territory's Sahtu region, where almost all of its oil and gas activity is occurring, currently has no highway connecting it to northern parts of the territory.
"The government is right now focusing on the Inuvik-Tuk highway because the federal government dropped $200 million into our coffers," he said. "The federal government is dictating where the priority is, even though right now the hot spot is in the Sahtu with the oil and gas exploration."
A senior government source played up the economic benefits in an email to CBC News. "The Inuvik to Tuktoyaktuk highway will complete Canada’s road network from coast to coast to coast, and will create jobs, economic growth and long-term prosperity in the North."