Tracking land surface dynamics over cloud prone areas with complex mountainous terrain is an important challenge facing the Earth Science community. One such region is the Lake Kivu region in Central Africa. We developed a processing chain to systematically monitor the spatio-temporal land use/land cover dynamics of this region over the years 1988, 2001, and 2011 using Landsat data, complemented by ancillary data. Topographic compensation was performed on Landsat reflectances to avoid the strong illumination angle impacts and image compositing was used to compensate for frequent cloud cover and thus incomplete annual data availability in the archive. A systematic supervised classification was applied to the composite Landsat imagery to obtain land cover thematic maps with overall accuracies of 90% and higher. Subsequent change analysis between these years found extensive conversions of the natural environment as a result of human related activities. The gross forest cover loss for 1988–2001 and 2001–2011 period was 216.4 and 130.5 thousand hectares, respectively, signifying significant deforestation in the period of civil war and a relatively stable and lower deforestation rate later, possibly due to conservation and reforestation efforts in the region. The other dominant land cover changes in the region were aggressive subsistence farming and urban expansion displacing natural vegetation and arable lands. Despite limited data availability, this study fills the gap of much needed detailed and updated land cover change information for this biologically important region of Central Africa. These multi-temporal datasets will be a valuable baseline for land use managers in the region interested in developing ecologically sustainable land management strategies and measuring the impacts of biodiversity conservation efforts.