The Mara River basin in East Africa is a trans-boundary river basin that highlights many of the development and conservation challenges in East Africa. The Mara River flows from its headwaters in the Mau Forest of Kenya through the northern portion of the Serengeti-Mara Ecosystem and into Lake Victoria in Tanzania, where it forms part of the headwaters of the Nile River basin. Changes in land use and landcover in the basin have raised concerns about the quality and quantity of water in the Mara River. We analyzed sediment cores from the Mara Wetland (near the river’s outlet into Lake Victoria) to evaluate how sedimentation rates and sources have changed historically, through a period marked by major changes in human and livestock population densities, land use, and disease epidemics (rinderpest). We collected sediment cores in August 2015 along a transect through the Mara Wetland from the upstream reaches to Lake Victoria. Slices of sediment cores collected from four distinct regions of the wetland were age-calibrated using radiocarbon and lead-210 dating methods. Core slices were then analyzed for sediment sources using a sediment fingerprinting approach, nitrogen and carbon stable isotope signatures, and mercury. Our results suggest that ecological conditions in the Mara River basin were fairly stable over paleoecological time scales (2000-1000 years before present), but there has been a period of rapid change in the basin over the last 250 years, particularly since the 1960s, likely due to anthropogenic factors. We also observed that downstream effects of landcover and land use change can be exacerbated by increasing occurrence of extreme rainfall events in the region. The Mara Wetland likely plays an important role in mitigating the impact of those factors on Lake Victoria. This work was the result of a partnership between Yale University, the Cary Institute of Ecosystem Studies, WWF-UK, WWF-Kenya and WWF-Tanzania.