Wetlands are areas of high biodiversity and provide many ecosystem services of high value. However, they are under constant threat from intense anthropogenic pressures, mainly agriculture intensification, urbanization, pollution, and climate change. The temporal and spatial patterns of land use/land cover (LULC) changes within eleven large wetlands in Greece were analyzed based on thematic maps generated from aerial orthophotos taken in 1945, 1975, and 2007. Socio-economic developments and the consequent need for more arable land and utilization of water resources are among the factors that mainly determine their evolution. In 2007, LULC classes related to wetland vegetation were reduced to one third as compared to 1945 and they were mainly replaced with croplands and urban infrastructures. Each of the different sub-periods that was considered (1945–1975 and 1975–2007) was distinguished by characteristic patterns of change. Agricultural land increased up to 42% from 1945 to 1975 and became the dominant LULC class in all deltaic areas but Evros. A considerable stability was observed for the period 1975–2007 for all LULC classed but it is remarkable the extent of urban areas that doubled. There is a tendency of landscape simplification and homogenization among the deltaic areas and the output of Markov chain analysis indicates that future composition of deltaic landscapes will be similar to the current one if the main driving forces remain constant. Changes in LULC composition and structure are also combined with coastal erosion in all deltaic areas. This is attributed to the modification of sedimentary deposits due to dam construction. The results summarize the change trajectories of the major deltaic areas in Greece from 1945 to 2007 thus offering a great outlook of changes that allows managers to understand how policies and socio-economic requirements affect the deltaic ecosystems and what decisions should be made to protect and enhance them.