The etymology of the name of the village comes from the ancient chapel dedicated to the evangelist Mark, also depicted in the civic coat of arms. On its origin there are controversial theories: the most legendary one believes that the country was founded by veterans of the sixth crusade, freed by Frederick II, after the Capture of Jerusalem, in the year 1228. The bas-relief of late Byzantine style of the Madonna di Giosafat located in the church annexed to the homonymous convent of the Capuchins, a few kilometers from the village, proved this thesis.
In 1369 the country is mentioned for the first time in a document as an autonomous community. In 1441 San Marco was entrusted, by King Alfonso I of Aragon, to Leone di San Agapito, coming from a noble family of Lucera. In 1637 the fief of San Marco became a duchy controlled by Francesco Gaetani d'Aragona. The duchy was then inherited by the Pignatelli family who kept it until 1821 and to whom it is due the construction of the Ducal Palace, now under restoration, under whose walls every August 21 takes place the Giostra della Jaletta.
The urban layout of the old town is well preserved and is characterized by cinant: narrow alleys with steep steps that connect two roads at different levels. In these alleys there are typical houses, modest houses generally developed on two floors and usually with two rooms: the real house, which is accessed from the main entrance; and the "low", which is accessed from a secondary door adjacent. Among the low houses stands the bulk of the Mother Church dedicated to San Nicola di Mira.
San Marco is surrounded by the green of the Bosco di San Cristoforo and the waters of the artificial lake of Occhito: just in its territory, near the bridge with 13 arches the fortress begins to fill the valley because of the barrier placed many km to the north, in the territory of Carlantino.