Sales began on July 4th at Great Smoky Cannabis Company within the Eastern Band of Cherokee Indians' land. This is located near Asheville.
With about 14,000 members, the Eastern Band can pass rules permitting cannabis as a sovereign nation and federally recognized tribe.
While many in the region say they support recreational sales, they worry people will buy it and take it outside tribal land. Marijuana remains illegal in the state.
Republican U.S. Sens. Thom Tillis and Ted Budd have raised concerns with federal and state law enforcement about whether drug laws will continue to be carried out in light of the dispensary.
A statewide medical marijuana bill has been considered in recent years by the North Carolina General Assembly.
WATCH | NC lawmakers consider legalizing medical marijuana
NC lawmakers consider legalizing medical marijuana
'Change the trajectory'
Starting in April, medical marijuana can be purchased on Cherokee land in North Carolina.
Adults at least 21 years of age with a tribal medical cannabis patient card or an out-of-state approved medical marijuana card can purchase items at Great Smoky Cannabis Co.
Hundreds of people, many with approved medical patient cards to purchase items, celebrated the historic opening of the dispensary on April, or '420 Day'.
The ceremony marks the latest liberalization of marijuana rules by the tribe, which in 2021 decriminalized possession of small amounts of marijuana within its 89 square miles (231 square kilometers) of land in the Blue Ridge Mountains.
The tribe also formed a medical marijuana system that included a tribe-created business to grow cannabis and sell it, reaping financial rewards for the tribal members and assisting those with medical conditions.
"This project will change the trajectory of their lives forever," Forrest Parker, general manager for Qualla Enterprises, the tribal company that manages the dispensary, said during the opening ceremony. "It will be a conduit to generations of social, economic and spiritual growth, unlike anything that's ever been witnessed."
The dispensary could generate over $200 million in gross sales revenues in its first year if limited to medical patients, compared with $385 million if the product is available to all adult users, according to figures from Qualla Enterprises released before last year's adult-use referendum.
The Associated Press contributed to this report.