Societal Impact Statement Infestation by the parasitic plant Striga hermonthica is a severe threat to food security in sub-Saharan Africa, impacting the production of the major staple crops pearl millet and sorghum, equating to 7–10 billion $ losses. Using Striga seed dependency on host-released germination stimulants, we have developed and validated a method for addressing the problem of accumulated parasite seedbanks—the major obstacle in combating Striga infestation in African rain-fed fields. Application of our method promises to alleviate the problem posed by this pernicious weed by increasing crop production for smallholder farmers. Summary The root parasitic plant Striga hermonthica is a major threat to global food security, causing enormous losses in yields of the main staple crops in sub-Saharan Africa, which include pearl millet, sorghum, maize and rice. Sustainable Striga control should ideally lead to the depletion of the vast, long-lived Striga seedbank, and this can be achieved by inducing suicidal seed germination through application of strigolactone (SL) analogs in the absence of host plants. However, this “suicidal germination” strategy has not been evaluated under the natural rain-fed conditions that prevail in Striga-prone regions. We have developed and validated a protocol for suicidal germination in laboratory and natural conditions in Striga-infested rain-fed African fields. Three SL analogs were tested and these resulted to between 65% and 55% reduction in Striga emergence in pearl millet and sorghum fields, respectively. We conclude that suicidal germination is an effective method for reducing the Striga seedbank. Moreover, the minimal demands of our protocol, in terms of water consumption and amount of selected SL analogs, make it affordable and applicable at a large scale in African rain-fed agriculture, holding promise for sustainable cleaning of heavily Striga-infested fields in sub-Saharan Africa.