The fire broke out about 12:03 a.m., WYTV-TV, Youngstown, reported. The names of the man and children, ages 11, 8 and 5, were not released, the TV station said.
The man's girlfriend, who also lived at the residence, placed an emergency call that summoned firefighters.
East Liverpool Fire Chief Chief William Jones said crews were at the scene within 5 minutes after receiving the call, but were confronted by intense flames.
"They made several attempts. They put ladders up to the second floor windows to try to get people upstairs," Jones said.
"I've been on the department 21 years. This is the first multiple fatality greater than two."
WFMJ-TV, Youngstown, said the state fire marshal's office was investigating the cause of the blaze.