The storm, which has killed two people in the Caribbean and led to extreme weather warnings all the way up the eastern seaboard of the US, crossed onto land at 23.10pm EDT (4.10am BST) about 40 miles south of Wilmington.
Isaias had previously been downgraded to a tropical storm, but sped up just before hitting the coast and was reclassified a hurricane late on Monday.
The National Hurricane Centre warned people living on the coast to brace for a storm surge up to 1.5 metres and up to 20cm of rain as the newly strengthened Isaias moved up the coast.
There had been fears Florida would be badly affected after Isaias killed two in the Dominican Republican and Puerto Rico, but the storm remained at sea as it brushed past Florida over the weekend, providing some welcome relief to emergency managers who had to accommodate mask-wearing evacuees in storm shelters.
But the Hurricane Centre has warned the danger has not passed.
Daniel Brown, senior hurricane specialist, said: "All those rains could produce flash flooding across portions of the eastern Carolinas and mid-Atlantic, and even in the northeast US."
A tropical storm warning extended all the way up to Maine, where flash flooding was possible in some areas on Wednesday.
The centre also warned of possible tornadoes in North Carolina on Monday night and early Tuesday, and from eastern Virginia to southern New England later on Tuesday.
President Donald Trump described Isaias as "very serious" on Monday.
"Storm surge and inland flooding are possible and everyone needs to remain vigilant until it passes," Mr Trump said.
Authorities in Myrtle Beach, South Carolina, ordered swimmers out of the water to avoid rough surf and strong rip currents.
By nightfall, power began to flicker at beachfront hotels as Isaias crossed the last bit of warm water on its path towards the US mainland.
Isaias is the ninth named storm of the year so far in the US, and North Carolina declared a state of emergency on Friday ahead of its arrival.
"North Carolinians have had to dig deep in recent months to tap into our strength and resilience during the pandemic," Governor Roy Cooper told a news conference on Monday. "That hasn't been easy.
"But with this storm on the way, we have to dig a little deeper. Let's keep each other safe from the wind and water as well as from the virus."