Quantifying how multiple ecosystem services and functions are affected by different drivers of Global Change is challenging. Particularly in African savanna regions, highly integrated land-use activities created a landscape mosaic with flows of multiple resources between land use types. A framework is needed that quantifies the effects of climate change, management and policy interventions on ecosystem services that are most relevant for rural communities, such as provision of food, feed, carbon sequestration, nutrient cycling and natural pest control. In spite of progress made in ecosystem modelling, data availability and stakeholder interactions, these elements have neither been brought together in an integrated framework, nor evaluated in the context of real-world problems. Here, we propose and outline such framework as developed by a multi-disciplinary research network, the Southern African Limpopo Landscapes network (SALLnet). Components of the framework such as the crop model APSIM and the vegetation model aDGVM2 had already been parameterized and evaluated using data sets from savanna regions of eastern, western and southern Africa, and were fine-tuned using novel data sets from Limpopo. A prototype of an agent-based farm household model was developed using comprehensive farm survey information from the Limpopo Province of South Africa. A first test of the functionality of the integrated framework has been performed for alternative policy interventions on smallholder crop-livestock systems. We discuss the versatile applicability of the framework, with a focus on smallholder landscapes in the savanna regions of southern Africa that are considered hotspots of global change impacts.