Parasitic weeds pose increasing threats to rain-fed rice production in Africa. Most important species are Striga asiatica, S. aspera and S. hermonthica in rain-fed uplands, and Rhamphicarpa fistulosa in rain-fed lowlands. Information on the regional spread and economic importance of parasitic weeds in cereal production systems is scant. This article presents the first multi-species, multi-country, single-crop impact assessment of parasitic weeds in Africa. A systematic search of public international and national herbaria and the scientific literature was conducted to collect all available data on the regional distribution, incidences and related yield losses of the most important parasitic weeds in rice. Herbaria specimens were geo-referenced and these coordinates were overlapped with rain-fed rice areas. Probabilistic diffusion waves of parasitic weeds were generated to derive most likely incidence values. Estimates from this spatial analysis were then combined with secondary data from the literature into a stochastic impact assessment model to generate a confidence interval of the likely economic impact per country and for sub-Saharan Africa as a whole. Rhamphicarpa fistulosa occurs in at least 36 African countries, 28 of which produce rice in rain-fed lowlands where this species thrives. Striga hermonthica is found in at least 32 countries, Striga asiatica in at least 44 and S. aspera in at least 17. A total of 50 countries have at least one of these three species of Striga, 31 of which produce rice in the rain-fed uplands where these species can be encountered. An estimated 1.34 million ha of rain-fed rice is infested with at least one species of a parasitic weed in Africa. Our stochastic model estimates that annual economic losses inflicted by all parasitic weeds exceeds, with 95% certainty, a minimum value of US $111 million and most likely reaches roughly US $200 million and increases by US $30 million annually. To reverse this trend and support small-holder rice farmers in Africa with effective, sustainable and affordable solutions for control, targeted investments in research, development and capacity building are required. The top-10 priority countries where such investments would probably have the highest return are Nigeria, Guinea, Mali, Côte d’Ivoire, Cameroon, Tanzania, Madagascar, Uganda, Sierra Leone and Burkina Faso.