Their release is the latest in a series of transfers out of the controversial facility as President Barack Obama works toward his goal of shutting it. Mr Obama established an task force to review prisoner cases there in 2009.
The Defence Department identities them as Mohammed Zahir, Shawali Khan, Abdul Ghani and Khi Ali Gul, who have all been returned to Afghanistan.
Eight Afghans are among the 132 detainees remaining at Guantanamo.
This was the largest single prisoner release from the military facility since 2009.
The release of the current four inmates also follows the publication of a report into 'enhanced interrogation techniques' used on detainees, who were subjected to waterboarding, simulated drownings and even 'rectal feeding' at 'black-site' prisons.
Some of those subjected to enhanced interrogation techniques were transferred to Guantanamo Bay when the black sites were closed.