Firefighters responded to reports of fire at a two-story house at 24 Warren Road at about 7:35 p.m., according to the San Mateo Fire Department.
First arriving units reported a fully-involved structure fire and requested a second alarm response, the fire department said.
Eight engines and 41 fire personnel responded to the emergency.
The fire was declared under control in about an hour and a half, the department said.
No residents were home at the time.
Two firefighters suffered minor injuries and were take to local hospitals for treatment, according to the fire department.
The blaze caused an estimated $700,000 in damage.
The cause remains under investigation.