Flames were coming through the roof of the one-story building in the 1000 block of Madison Avenue when firefighters arrived shortly after 12:45 p.m., Redwood City fire battalion chief Stan Maupin said.
The duplex consists of two units separated by a garage area, where it appears the fire started, Maupin said.
Firefighters confined the blaze to the garage and had it under control in about 45 minutes, he said.
Forty-six firefighters responded, and the response included eight engines and two ladder trucks.
No one was injured or displaced by the blaze, Maupin said. One of the units was vacant at the time of the fire.
Investigators are working this afternoon to determine the cause of the fire and extent of the damage.