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Protected areas are an essential tool for conserving biodiversity. However, their ecological effectiveness is contested and their capacity to resist human pressures differ. This dissertation aimed to assess the ecological effectiveness of different protection levels (from strict to less strictly protected: national park, game reserve, forest reserve, game-controlled area, and unprotected areas) in biodiversity (both mega diverse butterflies and mammals), maintaining habitat connectivity, and reducing anthropogenic threats at the wider landscape in the Katavi-Rukwa Ecosystem of southwestern Tanzania. To achieve this overarching goal, the researcher employed an interdisciplinary approach. First, he analyzed butterfly diversity and community composition patterns across protection levels in the Katavi-Rukwa Ecosystem. He found that species richness and abundance were highest in the game reserves and game-controlled areas, intermediate in the forest reserves, national park and unprotected areas. Species composition differed significantly among protection levels. Landscape heterogeneity, forest cover, and primary productivity influenced species composition. Land-use, burned areas, forest cover, and primary productivity explained the richness of species and functional traits. Game reserves hosted most indicator species. Second, the author modelled the spatial distribution of six large mammal target species (buffalo Syncerus caffer, elephant Loxodonta africana, giraffe Giraffa camelopardalis, hartebeest Alcelaphus buselaphus, topi Damaliscus korrigum, and zebra Equus burchellii) across environmental and protection gradients in the Katavi-Rukwa Ecosystem. Based on species-specific density surface models, he found relatively consistent effects of protection level and land-use variables on the spatial distribution of the target mammal species: relative densities were highest in the national park and game reserves, intermediate in forest reserves and game-controlled areas and lowest in un-protected areas. Beyond species-specific environmental predictors for relative densities, the results highlight consistent negative associations between relative densities of the target species and distance to cropland and avoidance of areas in proximity to houses. Third, the author examined temporal changes in land-use, population densities and distribution of six large mammal target species across protection levels between 1991 and 2018. During the surveyed period, cropland increased. Wildlife densities of most, but not all target species declined across the entire landscape. Based on logistic regression models, target species preferred the national park over less strictly protection levels and areas distant to cropland. Fourth, he quantified land-use changes, modelled habitat suitability and connectivity of elephant over time across a large protected area network in southwestern Tanzania. Based on analyses of remotely-sensed data, cropland increased from 7% in 2000 to 13% in 2019. Based on ensemble models, distance from cropland influenced survey-specific habitat suitability for elephant the most. Despite cropland expansion, the locations of the modelled elephant corridors (n=10) remained similar throughout the survey period. Based on circuit theory, the author prioritizes three corridors for protected area connectivity. Key indicators of corridor quality varied over time, whereas elephant movement through some corridors appears to have increased over time. Overall, this dissertation underpins differences in ecological effectiveness of protected areas within one ecosystem. It highlights the need to utilize a landscape conservation approach to guide effective conservation across the entire protection gradient. It also suggests the need to enforcing land use plans and having alternative and sustainable forms for generating income from the land without impairing wildlife habitat.