<title>Abstract</title> Sweetpotato, <italic>Ipomoea batatas</italic> (L.) Lam. (2n = 6x = 90), is among the world’s most important food crops and is North Carolina’s most important vegetable crop. The recent introduction of <italic>Meloidogyne enterolobii</italic> poses a significant economic threat to North Carolina’s sweetpotato industry and breeding resistance into new varieties has become a high priority for the US sweetpotato industry. Previous studies have shown that ‘Tanzania’, a released African landrace, is resistant to <italic>M. enterolobii.</italic> We screened the biparental sweetpotato mapping population, ‘Tanzania’ x ‘Beauregard’, for resistance to <italic>M. enterolobii</italic> by inoculating 246 full-sibs with 10,000 eggs each under greenhouse conditions. ‘Tanzania’, the female parent, was highly resistant, while ‘Beauregard’ was highly susceptible. Our bioassays exhibited strong skewing toward resistance for three measures of resistance: reproductive factor, eggs per gram of root tissue, and root gall severity ratings. A 1:1 segregation for resistance suggested a major gene conferred <italic>M. enterolobii</italic> resistance. Using a random-effect multiple interval mapping model, we identified a single major QTL, herein designated as qIbMe-4.1, on linkage group 4 that explained 70% of variation in resistance to <italic>M. enterolobii.</italic> This study provides a new understanding of the genetic basis of <italic>M. enterolobii</italic> resistance in sweetpotato and represents a major step towards the identification of selectable markers for nematode resistance breeding.