In this study we studied 22 maize genotypes, with a diversity of origins, across field locations in Kenya (one season) and Malawi (two seasons), and in the greenhouse in Wageningen. We identified new maize genotypes with effective broad-spectrum resistance against the parasitic weed Striga, a prevalent biological constraint to crop production on the African continent. Resistance against S. hermonthica (the predominant Striga species north of the equator) is also effective against S. asiatica (predominant south of the equator). For each maize genotype we profiled the strigolactone production levels in the root exudates, as genetic variation in strigolactone production is assumed to be an important resistance mechanism. We however found a rather weak correlation between genotypic strigolactone production, assessed in the greenhouse and lab, and Striga infection levels assessed in the field, suggesting the presence of (an) other resistance mechanism(s). In the field, across sites we also studied the relation between Striga infection and maize yields. When high Striga infection (partly determined by seasonal rainfall distribution) coincides with overall low rainfall, we observed that Striga resistance mitigates drought impacts on maize yields. In seasons of low Striga-infection or more favorable rainfall, other factors (e.g., local adaptation, growth duration, yield potential) appear more important determinants for maize yield. We discuss the implications of these findings for maize breeding.