The suspected gunman was later found dead of a gunshot wound in the driver's seat of a stopped car, Jonesboro police Sergeant Doug Formon said at a news conference. It was not immediately clear if the gunshot was self-inflicted.
Formon said a man and a 13-year-old girl were killed on Saturday afternoon inside the home in Arkansas, where it appeared a family was having a party or gathering.
Four other people were injured and were taken to hospitals. Formon said the children, ages 8 and 10, were transported in critical condition.
Police received a call about the shooting at the home and later responded to a report of a second shooting at a business, where Forman said the worker was found shot to death.
Formon said a farmer or passing motorist later called to report a car parked in the middle of a county road.
A deputy responded and found the stopped car with the suspected gunman inside.
Forman said that police did not know of a motive and that the investigation is ongoing.
He declined to identify the victims or the suspect, saying officials wanted to be sure all family members had been notified. He said it was not known if the suspect and victims were related.