The Prokopos Lagoon is part of the Kotychi Strofilias National Wetlands Park, which is supervised by the Ministry of Environment, Energy and Climate Change of Greece. The lagoon is situated at the northwestern coast of the Peloponnese and is protected by the Ramsar Convention. It is an important ecosystem with ecological services providing habitats for many plants and animals and essential goods and services for humans as well. No previous relevant studies for the wider wetland area are available, and given that lagoons are important ecosystems, their diachronic evolution should be under constant monitoring. Using remote sensing techniques in Geographic Information System (GIS) environment, alterations in critical parameters could be measured and applied for the protection of the area. The present study examines the spatiotemporal changes of the water extent of the Prokopos Lagoon, estimating landscape metrics and several morphometric parameters and indices related to the geomorphological features of the lagoon for the 1945–2021 period. Moreover, the adjacent shoreline was studied for each past decade evolution from 1945 to present, and it is discussed to whether there is a relationship between shoreline changes and the lagoon. High resolution satellite images and air photos at scale 1:30,000 were used to digitize the shorelines and the polygons of the lagoon’s surface. Linear Regression Rates (LRR), Net Shoreline Movement (NSM), End Point Rate (EPR) and Shoreline Change Envelope (SCE) provided by the Digital Shoreline Analysis System (DSAS) were used to determine the changes. Finally, future shoreline positions for 2021 and 2031 are estimated, while based on statistic models, we found that in the coastal area, the erosion–accretion cycle is predicted to be completed in 2031, after almost 86 years since 1945.