<p>The root-knot nematode (RKN), <i>Meloidogyne incognita</i>, is a major pathogen that infects the roots and severely reduces yield of several important food crops, including sweetpotato (<i>Ipomoea batatas</i> Lam.). The molecular mechanisms of plant resistance to RKN infection remain unclear. Differences between the responses of susceptible and resistant sweetpotato cultivars to RKN invasion have been identified previously using transcriptomic analysis based on RNA sequencing. The current study analyzed changes in gene expression during the differential resistance response to RKN infection in the sweetpotato cultivars Danjami (DJM), Pungwonmi (PWM), and Juhwangmi (JHM) that are resistant to RKN. Genes that were differentially regulated in two or more cultivars upon infection were identified. Pairwise comparisons showed that DJM and JHM shared the highest number of differentially regulated genes, while PWM and JHM shared the lowest. Cultivar-specific expression patterns of defense- and hormone-related genes were identified. DJM showed activation of cell wall modification, GLU, R genes, and WRKY TFs, while PWM upregulated redox regulation, GST, HSPs, and SA signaling. In contrast, JHM uniquely activated GST and auxin signaling but repressed genes related to secondary metabolism and HSPs, reflecting distinct resistance strategies. The analysis identified genes that showed expression changes specific to a single cultivar in response to infection, suggesting that resistance to RKN infection was mediated through both common and cultivar-specific pathways. These findings increase the understanding of the resistance response to RKN invasion in sweetpotato roots and provide useful information for further studies of plant defense mechanisms.</p>