Tawoos Khan, the governor of Khan Shine district of Helmand province about 675 kilometres south of Kabul, came under attack on his way to the district.
"Today at 10.00 am the Khan Shine district governor was ambushed en route to the district and killed with his four bodyguards," provincial spokesman Mohammed Wali told AFP.
Two other people were injured.
No one was arrested in relation to the incident, but Wali claimed Taleban remnants were responsible for the attack.
A man identifying himself as the spokesman for the ousted Taleban regime, Abdul Latif Hakimi, called AFP from an undisclosed location and claimed responsibility for the attack.