Resistance to root-knot nematodes [Meloidogyne arenaria (Neal) Chitwood] is needed for cultivation of peanut in major peanut-growing areas, but significant resistance is lacking in the cultivated species (Arachis hypogaea L.). Markers to two closely-linked genes introgressed from wild relatives of peanut have been identified previously, but phenotypic evidence for the presence of additional genes in wild species and introgression lines has eluded quantitative trait locus (QTL) identification. Here, to improve sensitivity to small-effect QTLs, an advanced backcross population from a cross between a Florunner component line and the synthetic amphidiploid TxAG-6 [Arachis batizocoi x (A. cardenasii x A. diogoi)]4x was screened for response to root-knot nematode infection. Composite interval mapping results suggested a total of seven QTLs plus three putative QTLs. These included the known major resistance gene plus a second QTL on LG1, and a potentially homeologous B-genome QTL on LG11. Additional potential homeologs were identified on linkage group (LG) 8 and LG18, plus a QTL on LG9.2 and putative QTLs on LG9.1 and 19. A QTL on LG15 had no inferred resistance-associated homeolog. Contrary to expectation, two introgressed QTLs were associated with susceptibility, and QTLs at some homeologous loci were found to confer opposite phenotypic responses. Long-term functional conservation accompanied by rapid generation of functionally divergent alleles may be a singular feature of NBS-LRR resistance gene clusters, contributing to the richness of resistance alleles available in wild relatives of crops. The significance for peanut evolution and breeding is discussed.