Galerius (260-311) was born in Serdica and was initially a herdsman like his father, before going on to join the Roman army, where he served with distinction under Emperors Aurelian and Probus. When the Tetrarchy was established in 293, he was named as one of the junior co-emperors alongside Constantius, marrying Emperor Diocletian's daughter Valeria.

Galerius fought alongside his father-in-law against the resurgent Sassanid Empire, eventually leading to his sacking of the capital Ctesiphon and his capture of the wife and children of the Sassanid king Narseh, with which he was able to negotiate a long-lasting and favourable peace treaty. When Diocletian and Maximian abdicated in 305, Galerius and Constantius became joint emperors, with Galerius conspiring to secure a stronger power base than his co-ruler. His hopes and plans came to naught when Constantius died a year later and his son, Constantine I, ascended to become emperor of the western half of the empire.

Galerius had been a staunch opponent of Christianity, supposedly prodding Diocletian into enacting the Diocletianic Persecution, the largest and most violent official persecution of Christians in the empire's history, by burning down the Imperial Palace and blaming it on Christian saboteurs. His attitude changed in 311 when he enacted the Edict of Toleration, asking for Christians to pray for him as he suffered through a painful and fatal illness. He died six days later.