Resistance to root-knot nematodes [Meloidogyne incognita (Kofoid & White) Chitwood] in sweetpotato [Ipomoea batatas (L.) Lam.] was studied in a mapping population consisting of 240 progeny derived from a cross between ‘Beauregard’, the predominant cultivar in the United States, and ‘Tanzania’, an African landrace. Quantitative trait loci (QTL) analyses to locate markers associated with resistance to root-knot nematodes (RKN) were performed using genetic maps based on parental segregation in ‘Beauregard’ and ‘Tanzania’ consisting of 726 and 947 single-dose amplified fragment length polymorphism (AFLP) markers, respectively. RKN resistance in the progeny was highly skewed with most of the progeny exhibiting medium to high levels of resistance. Single-point analysis of variance and interval mapping revealed seven consistently significant QTL in ‘Tanzania’ and two significant QTL in ‘Beauregard’. In ‘Tanzania’, three QTL were associated with reduction in resistance as measured by the number of RKN egg masses and explained ≈20% of the variation. Another four QTL had positive effects on resistance and explained ≈21% of the variation. Other minor QTL explained ≈2% or less of the variation but were not always consistent across geographical locations. In ‘Beauregard’, two QTL had positive effects on RKN resistance and explained ≈6% of the observed variation. Based on molecular and phenotypic data, RKN resistance in sweetpotato is hypothesized to be conferred by several genes, but at least nine AFLP markers (seven from ‘Tanzania’ and two from ‘Beauregard’) are associated with genomic regions that have the biggest effect in the number of egg masses of RKN produced in the root system.