Authorities ordered the evacuation of about 88,000 people, including the entire city of Fort McMurray, the Regional Municipality of Wood Buffalo said. Reception centers for evacuees were being set up in Edmonton.
A state of emergency across the province was declared later in the day.
The blaze has already destroyed 80% of Fort McMurray's Beacon Hill community, RM Wood Buffalo said.
The wildfire began Sunday and had torched 24,710 acres by Wednesday, CNN partner CBC News
said. The cause of the blaze remains unclear.
In all, some 1,600 structures have been destroyed by the fire, Alberta Premier Rachel Notley said. However, there have been no reports of deaths or injuries, officials said.
High winds, warm weather and dry conditions were expected to create "explosive conditions" for fire growth and make it difficult for firefighters to keep up, Alberta forestry manager Bernie Schmitte said.
The fire is "challenging all of us," he said.
About 250 firefighters were on the ground, while the skies are saturated with anti-fire aircraft.
Paul Spring said his neighborhood went down in flames.
"The whole subdivision is gone," the longtime pilot and firefighter said. "Things are pretty horrible right now. We've been out flying and surveying the damage."
Spring is the president of Phoenix Heli-Flight. Despite his loss, he hasn't stopped working.
He said his team will fly firefighting missions, dropping water and assisting crews on the ground.
"As long as we keep the people safe, we can rebuild the houses," he said.
Faith Johnston, who evacuated to Edmonton, recalls the tense moments her family was forced to leave when the fire began approaching her apartment on Tuesday.
"It was the most terrifying feeling looking straight ahead at a wall of flames 10 times higher than us," she told CNN in an email exchange.
Johnston was able to record the first few moments. But she stopped because conditions became too terrifying.
"I was in a complete state of shock and fear."
The thick smoke made it hard to see. "The streets were in a panic, people were abandoning their vehicles and hitchhiking," she said.
The dangerous mix of extreme temperatures and bone-dry conditions means firefighters are battling "explosive" conditions.
"All our efforts to control and contain the fire were challenged by this extreme fire behavior," Schmitte said. "Efforts were also hampered by smoke conditions. Basically fire behavior was beyond all control efforts."
The good news: "Conditions are set to improve over the next couple of days," CNN meteorologist Judson Jones said.
Temperatures that soared to 32.6 Celsius (90.6 degrees Fahrenheit) on Tuesday will drop to the low 20s C (60s F) on Thursday and Friday -- giving firefighters a hand in combating the blaze, Jones said.
The main challenge ahead: fierce winds gusting in different directions.
"If it's constantly changing direction in different ways, it's hard to control a fire," Jones said.
Driving through a blanket of smoke
Jordan Stuffco filmed the exodus out of Fort McMurray. Drivers plowed through thick clouds of black smoke as flames shot up nearby.
"My harrowing drive evacuating #ymm praying for my friends," Stuffco tweeted.
YMM is the airport code for Fort McMurray.
The only hospital in the city, Northern Lights Regional Health Centre, evacuated all 105 patients, the Alberta government said.
"I am out. I am safe," tweeted one resident. "I've never been more scared in my life. Praying for my home right now."
Spring, the helicopter pilot who lost his home, said his company has been scrambling to fly patients from the evacuated hospital to other medical facilities.
Mark Jones told CNN his neighborhood went from a voluntary evacuation to a mandatory one in an hour.
"It took me about three hours to get out of town," he said. "Once the evacuation started, everything was in gridlock. Traffic was going in one direction. There were people going in ditches and everywhere."
Prime Minister Justin Trudeau said the country stands ready to help.
"Canada's a country where we look out for our neighbors," he said. "We are there for each other in difficult times."
He said those wanting to help can donate to the Canadian Red Cross