This study aims to quantify the landscape spatio-temporal dynamics including Land Use/Land Cover (LULC) changes occurred in a typical Mediterranean ecosystem of high ecological and cultural significance in central Greece covering a period of 9 years (2001–2009). Herein, we examined the synergistic operation among Hyperion hyperspectral satellite imagery with Support Vector Machines, the FRAGSTATS® landscape spatial analysis programme and Principal Component Analysis (PCA) for this purpose. The change analysis showed that notable changes reported in the experimental region during the studied period, particularly for certain LULC classes. The analysis of accuracy indices suggested that all the three classification techniques are performing satisfactorily with overall accuracy of 86.62, 91.67 and 89.26% in years 2001, 2004 and 2009, respectively. Results evidenced the requirement for taking measures to conserve this forest-dominated natural ecosystem from human-induced pressures and/or natural hazards occurred in the area. To our knowledge, this is the first study of its kind, demonstrating the Hyperion capability in quantifying LULC changes with landscape metrics using FRAGSTATS® programme and PCA for understanding the land surface fragmentation characteristics and their changes. The suggested approach is robust and flexible enough to be expanded further to other regions. Findings of this research can be of special importance in the context of the launch of spaceborne hyperspectral sensors that are already planned to be placed in orbit as the NASA’s HyspIRI sensor and EnMAP.