Samuel was the youngest of four brothers, the comitopuli, sons of a Bulgarian provincial governor who had built a new capital and a new state in the western Bulgarian highlands while the eastern half of the old First Bulgarian Empire was being absorbed by Constantinople. He was a soldier first and a king second; his armies had reached as far south as Corinth, raiding the Peloponnese. Basil II had become Byzantine emperor as a young man in 976. His first Bulgarian campaign, ten years later, ended with his army nearly destroyed in the Gates of Trajan pass. He was patient. Year after year he came back, taking Vidin, defeating Samuel at Skopje in 1004, peeling away the Bulgarian fortresses one by one. Bulgaria had run out of cities to lose.

Samuel chose Kleidion because he had to. His nobility was wavering; in 1005 even the governor of the major Adriatic port of Dyrrhachium had simply opened his gates to Basil. To force a battle on his own terms, Samuel funnelled the Byzantines into the narrow valley of the Struma River, fortified the slopes of Belasitsa, and waited. Basil's army marched the Via Egnatia from Constantinople through Komotini, Drama and Serres, came up the Rupel Pass, and turned into the Strumitsa valley. Bulgarian arrows came down from the wall and the Byzantine assaults came back broken. Samuel sent a relief army south under a noble named Nestoritsa to draw Basil off; it reached Thessaloniki and was defeated outside the city by the strategos Theophylact Botaneiates, who then marched north to join his emperor. Basil was now a man besieging a wall in a valley with reinforcements arriving and no easy way through.

Basil ordered his general Nikephoros Xiphias, governor of Philippopolis, to take a force up and over the high shoulder of Belasitsa by a steep mountain track that the Bulgarians had not adequately watched. While Basil resumed his attacks on the palisade from the front, Xiphias's men climbed the mountain and came down behind the Bulgarian line. The defenders of the wall, suddenly under attack from two sides, broke. In the confusion of the rout, thousands were killed in the valley. Samuel and his son Gabriel Radomir rode east from Strumitsa to try to rally the army, but in fighting near the village of Mokrievo in what is now North Macedonia they were nearly killed. Gabriel Radomir put his father on his own horse and bought him time to escape. The tsar reached Prilep; from there he travelled west to his palace at Prespa.

Skylitzes, the Byzantine chronicler, reports that Basil took fifteen thousand Bulgarian prisoners; another source says fourteen thousand; the Bulgarian translation of the Manasses Chronicle puts the number at eight thousand. Modern historians, including the Bulgarian scholar Vasil Zlatarski, have argued the higher figures are probably exaggerated. What is not in question is what Basil did with the men he took. He divided them into groups of one hundred. He ordered ninety-nine men in each group blinded. The hundredth man was left with one eye, so that he could lead the others home. The reason given by some Byzantine writers was retaliation for the death of Botaneiates, who had been ambushed and killed by Bulgarian raiders not long after Kleidion. Another reason offered, more coldly, was that Byzantine law treated rebels with mutilation, and that to Basil the Bulgarians were rebels. The columns of blinded men walked west through the valleys to find their tsar. When Samuel saw them, according to the chronicles, he had a stroke and died two days later, on 6 October 1014. He had ruled the western Bulgarian state for thirty-eight years.

The name Bulgar-Slayer — Boulgaroktonos in Greek — was applied to Basil only later. He himself does not seem to have used it. But the act of Kleidion entered the history of two peoples in different ways. For the Byzantines, it was the moment the long war turned. Within four years Bulgaria was a Byzantine province; it would not be independent again until the Asen brothers led a successful revolt in 1185. For Bulgarians, it became one of the foundational stories of national memory, told and retold and disputed, with the eight-thousand and fifteen-thousand figures and the cold mathematics of the hundredth man arriving in nearly every retelling. Samuel is buried, by tradition, at the church of St Achilleios on the small Greek island of Agios Achillios in Lake Mikri Prespa; his bones were found there in 1965. The valley of Kleidion is still farmed. Visitors can walk the ground; a memorial mound was raised at the site in 2014 for the millennium.