Harmanli arose around the 16th century. There are no remains of old settlements within the boundaries of today's Harmanli, but traces of the late Neolithic and Middle Roman era can be found in its nearby outskirts. Around 1510, a solid Kervan Sarai was built here, around which a Turkish population settled, and a state threshing floor was built near it. Intense and accelerated development and improvement of the city took place after 1580, and in 1833 a cell school was opened, in 1835 the church of "St. Athanasius" was built.

The liberation of the town of Harmanli from Turkish slavery took place on 17.01.1878, with a short but fierce battle with the local Turkish military units. After the Liberation, craft, shoemaking, wheel-smithing, and other workshops were established, as well as joint-stock companies for the purchase of tobacco.

The city's roadside location is the basis for the statement of the writer Gencho Stoev: "Harmanli does not need to travel, because the world passes through it."

On the right bank of the Harmanlii River, skilled craftsmen built a solid caravanserai. The purpose of this first representative building was to provide shelter for travelers and horses, as well as the peaceful journey of commercial and economic embassies along the great state road Constantinople - Belgrade. Here they find protection from the constant robber raids and the poor peasants from the surrounding villages. The settlement was named Harmanli after the spacious Sultan Harman.

In the 16th century, an arched bridge over the river in the Arab style common to the era was built. The marble inscription on the bridge reads: "The world is a bridge over which passes the road of the king and the pauper." The Humpback Bridge has been preserved almost intact to this day. At that time, the historic fountain of The spring of the white-legged (izvora na belonogata), half an hour's drive from the bridge, was also built. The legend of Gergana, immortalized in the wonderful poem of Petko R. Slaveikov, is intertwined with another legend, according to which the boyar Valkashin, the father of the legendary King Marko, died in a fight with the Turks near this spring. Although the subject of local lore controversy, even if only a fiction, the fountain is an emblem of Harmanli.