The fire appears to have started at Homework, a home decor and lifestyle store, or the business next door on the 1200 block of 3rd Avenue.
The Prince George Fire Department was called a little before 10 p.m., PT, and crews arrived to find smoke and flames coming from the buildings.
Adjacent businesses, including a popular restaurant, Nancy O's, were badly damaged by smoke and water, but fire officials said nobody was hurt.
Nancy O's co-owner Garrett Fedorkiw said he wasn't in the restaurant when the fire started.
"When I got the call and started driving downtown, from several hundred metres away you could see the smoke billowing in the air. It was at that point I knew it was quite serious," said Fedorkiw.
"It was a full restaurant — a band on stage — so thank God somebody noticed the fire in the initial stages, and we got everyone [out] right away," Fedorkiw said, "Nobody was hurt, and everybody got out, and it was a raging fire."
Local musician Eric Tompkins was performing at Nancy O's when the alarm was raised.
"We were playing some songs. Somebody said 'everybody get out, there's a fire!' and the place emptied out within about a minute," said Tompkins.
Assistant Fire Chief John Law said the back of the buildings suffered the most damage.
"We'll be investigating this to determine the cause and find out what took place," he said.
Wednesday night's fire came almost exactly a year after a fire tore through businesses on George Street, just a few blocks away.