The ruins of ancient Tarsus, the metropolis of the Cilicia Region, located in the south of Anatolia, lie under the modern city. Ancient authors talking about Tarsus also mention the Cydnus River, which runs through the middle of the ancient city. These authors also emphasize the size of the city and the level of prosperity it has achieved. On the basis of the development of the city, there are factors such as having a port in ancient times, the fact that an international road reaches the city and the location of the Cydnus River passing through the city. All these qualities also confirm that good planning was observed in the first establishment of the city. These characteristics of Tarsus must have significantly affected various areas such as urban planning, commercial and cultural development. Considering the location of Tarsus suitable for road, sea and river transportation, it becomes clear why it is defined as a large and rich city. Tarsus, which has a very strategic location, has water-related structures such as bridges, baths, and cisterns as well as many important structures. In addition, imported ceramics that will shed light on both the development of Tarsus and its commercial activities in the ancient period can be listed among the remarkable archaeological finds. In this study, the connection of the Cydnus River with the city, which flowed through the borders of Tarsus district in ancient times and was changed in the Eastern Roman (Byzantine) Period, was discussed. The contribution of the Cydnus River to trade, city planning and the welfare level of Tarsus since its foundation has been researched, based on the information provided by ancient and modern authors, as well as archaeological data.