The regional environmental–geochemical surveying of the long-term impacts of mining and ore processing on a large part of the Zambian Copperbelt mining district was carried out by the Czech Research Group with cooperation of the Geology Department, University of Zambia, and the Geological Survey of Zambia in the period 2002–2018. This included the characterization of various sources of contamination, the extent of contamination of soils and crops, and the degree of contamination of river water and sediments. Solid speciation studies of potentially harmful chemical elements (PHEs), plant and human bioaccessibility studies, and a range of mineralogical techniques were used to assess the pathways of PHE cycling in terrestrial and aqueous systems and their impacts on human health. Ores of the Zambian Copperbelt mining district are mined for Cu and Co, but a number of other trace elements (Pb, As, Cd, Hg, Pb, Zn) gradually accumulated in soils and stream sediments. It was concluded that the most important problems related to ore mining and processing are the contamination of soil and crops due to dust fall out from tailing facilities and emissions from smelters. Moreover, leakages of solutions from tailing dams, insufficient technological control of their stability and breakdowns on pipelines transporting slurry from treatment plants to tailing impoundments cause contamination of water courses and deposition of metal(loids) in stream sediments. However, the contamination of the Kafue River water is relatively limited due to its high neutralization capacity. In contrast, in some Kafue River tributaries, especially those close to big mining centers, the concentrations of dissolved Cu and Co are high (up to 14,752 μg/L and 1917 μg/L) and exceed Zambian effluent limits. We also recommend measures that could contribute to minimizing the impact of ore mining and processing on the environment and the health of the local population.