Officials say the shooting happened at a mobile home along Faison Highway.
It happened in the 2400 block of High House Road in Clinton.
After losing control and crashing near Kitty Fork, the motorcyclist drew his gun, leading the deputy to discharge theirs.
The Sampson County Sheriff's Office said a second person was also shot and remains in the hospital.
The eastbound lanes of I-40 from exit 348 to exit 355 in Sampson County are now open.
Three of the victims were airlifted from the scene.