The results of the research have revealed integrated effect of the mineral fertilizer application and protective measures influence on weed infestation and potato yield. This effect was developed on the second half of the vegetation and expressed in more stronger inhibition of plant development (from 36,6 to 20,4 and 11,1 g/m2 on low, medium and high levels of mineral nutrition, respectively), in the reduction of species diversity (from 12 to 10 and 10 species/m2) and number of weeds (from 69 to 42 and 32 species/m2). The highest biological (biomass reduction – 95,3%, the number of weeds – 79%) and economic (yield increase – 228 с/ha or 107%) effect was achieved by the high rates of mineral fertilizer application and combined protective measures of potato crops from weeds. This variant was characterized by the greatest profitability (125,3%), whereas chemical protection providing double treatment of potato plantings with herbicides, even at the middle and high level of mineral nutrition, was less effective (102,6 and 109%) in economic terms.