Being the only watershed in Metro Manila, the La Mesa Watershed (LWM) is susceptible to degradation due to its proximity to major urban centers. LMW experienced deforestation in the past, but this was addressed through various reforestation initiatives. This study used several landscape metrics to conduct a spatio-temporal analysis of land use/land cover changes and landscape structure in LMW. Four official land cover maps for the years 2003, 2010, 2015, and 2020 were obtained from NAMRIA and analyzed using QGIS. Change detection analysis was carried out using the change matrix technique. The study area was classified into eight land cover classes: open forest, brush/shrubs, grassland, annual crop, perennial crop, open/barren, built-up, and inland water. Open forest was identified as the dominant land cover in the watershed. The study detected an 8.76% decline in forest cover from 2003 to 2010, a 1.29% increase from 2010 to 2015, and a 2.08% increase from 2015 to 2020. On the analysis of landscape structure, while open forest remains relatively unfragmented in terms of the number of patches, an increase in edge density due to factors like urbanization or infrastructure development could potentially impact the quality of the open forest habitat, leading to habitat degradation and reduced core area. The results also confirmed that urbanization is still the major driver of changes in LMW. It is hoped that the result of this study provides input on the implementation of the Integrated Watershed Management Roadmap for Angat, Ipo, and La Mesa (IWMRAIL), and serves as a model for other watersheds seeking to undertake comprehensive land use and land cover analysis.