Coconino County officials declared an emergency after the "Tunnel Fire" rapidly grew from 100 acres to more than 9 square miles by the evening.
Fueled by whipping winds, Ponderosa pine trees and dry grass, the blaze ripped through two-dozen structures and forced residents of more than 700 homes to evacuate.
Large plumes of smoke were seen on the outskirts of Flagstaff and the fire was pushed over a major highway on Tuesday.
The wildfire shut down U.S. 89 and high winds grounded aircraft that could drop water and fire retardant.
Power was shut off to approximately 625 customers, according to Arizona Public Service Co.
Coconino County officials said during a Tuesday evening news conference that 1,000 animals were also evacuated and that more than 200 structures remain threatened.
While authorities had gone door to door telling people to leave, Coconino County Sheriff Jim Driscoll said firefighters and law enforcement officers had to pull out to avoid getting boxed in.
He said his office got a call about a man who was trapped inside his house, but firefighters couldn’t get to him.
"We don’t know if he made it out or not," Driscoll said.
Authorities won't be able to determine whether anyone was injured in the wildfire until the flames subside.
About 200 firefighters were fighting the fire and more are expected as a top-level national management team takes over later this week.
The fire is moving northeastward, away from Flagstaff and toward Sunset Crater Volcano National Monument, according to Coconino National Forest spokesman Brady Smith.
"It’s good in that it’s not headed toward a very populated area, and it’s headed toward less fuel," he said. "But depending on the intensity of the fire, fire can still move across cinders."
The fire is 0% contained, per InciWeb, and windy and dry conditions are expected throughout the week.
The fire started Sunday afternoon, although investigators don't yet know what caused it.
Elsewhere in Arizona, firefighters battled a wildfire in a sparsely populated area of the Prescott National Forest.
The National Interagency Fire Center reported Tuesday that nearly 2,000 wildland firefighters and support personnel were assigned to more than a dozen large wildfires in the southwestern, southern and Rocky Mountain areas.
The Associated Press contributed to this report.