Fire officials said flames broke out at the building on South Third Street and Wells Avenue South around 7:15 p.m.
Flames and plumes of black smoke were seen pouring out of the roof of the two-story building, which houses shops on the lower floor and apartments above them.
The blaze began burning in the basement and made its way through the roof, officials said. The building is said to be a total loss.
"The manager found the fire, found the room where the fire was, tried to put out with a fire extinguisher," said Renton Fire Chief Daniel Davis. "That didn't work too well. Called us."
"The room was compressed with smoke," said Roy Beeler, who first stumbled upon the flames. "From the moment I opened the door, all the hallways, I couldn't see instantly and I couldn't breathe. So I was feeling my way out, pounding on doors, yelling, 'Everybody, get out!'"
The flames forced dozens of residents to rush out of their apartments.
"I threw my cats in a suitcase and now, they're in my car," said Stephanie Swanson, who said she was in the shower when she was told to evacuate.
At one point the flames threatened the entire block but by 9:30 p.m. fire crews had gotten a handle on the fire, which was contained to the destroyed building. Several of the neighboring buildings sustained smoke and water damage, but no one was injured, officials said.
Andrew Johnson called his family as soon as he learned of the blaze. Johnson's family owns several of the buildings in the area.
"It's sad, it's sad. Those are all historic buildings. (They) might be in bad shape, but my family takes a lot of pride in those."
The cause of the fire has not been determined.
Fire crews from Renton, Tukwila, Kent, Skyway and Seattle battled the blaze.