In 1150, Ramon Berenguer IV⁽¹⁾ ceded the castle and territory of Amposta to the Order of the Hospital of St John. However, for this donation to take effect, the Knights Templar had to renounce the part of the territory that belonged to them by right of conquest, which they did three years later, in 1153, when they took possession of Miravet. At the time this agreement was signed, the Hospitallers had already established a convent in Amposta.

The document relating to the donation of Amposta mentioned a sum of money intended to cover the cost of converting the castle into a residence for the Hospitallers. This donation, together with the Order's installation in the castle and the arrival of settlers to occupy the land, would become the nucleus of the future town of Amposta, an important strategic location in the defence of Tortosa.

As soon as they settled there, the Hospitallers made Amposta an important administrative centre responsible for colonising, exploiting and administering the territories of the Ebro Delta and the area north of the Serra de Montsià.

With these rights in the Delta, in addition to fishing rights in the Tortosa area and the collection of tithes from the salt marshes granted to them by Count Ramon Berenguer IV, Amposa became one of the richest preceptories in the region.

The development of this significant economic influence is reflected in the fact that, as early as 1154, Amposta became the seat of the Catalan-Aragonese province of the Order of the Hospital. From then on, in addition to the commander of Amposta, the castle also housed the commander of the province, who bore the title of "Castellán d'Amposta".

As part of the defensive strategy for the mouth of the Ebro River, several towers performed military functions that complemented those of Amposta Castle. This was the case, among others, with two towers that were the subject of a dispute between the Knights Templar and the Knights Hospitaller, until in 1189 Alfonso II "the Chaste" demanded that the Knights Hospitaller prove that they belonged to them. These were probably towers located on the right bank of the Ebro, and one of them may even have been the tower of Carrova⁽²⁾, as the same conflict also concerned the use of water from the Carrova spring.

The advance of the Reconquista towards the south led to the decline of Amposta as a strategic site. Thus, around 1280, King Peter III "the Great" undertook to recover the estates that his predecessors had bequeathed to the Order of the Hospital. At that time, the Hospitallers exchanged their estate in Amposta with the King for estates further south, near Valencia. However, the Hospitallers retained several properties in Amposta, including the castle, which had lost its military function, and the parish church.