The root-knot nematodes (RKN) (Meloidogyne graminicola) are a devastating threat to rice worldwide. The cultivated germplasm is either susceptible or moderately resistant to rice RKN. Therefore, there is a need to identify resistance sources against M. graminicola as an eco-friendly management strategy. The present study evaluated the host response of Oryza sativa genotypes comprising basmati, non-basmati improved varieties, their advanced breeding lines (83) and Oryza glaberrima accessions (42) against M. graminicola in the nematode-infested plot for two consecutive years. All O. sativa genotypes exhibited susceptible responses, while O. glaberrima accessions showed variable levels of resistance. Three of the O. glaberrima accessions (IRGC102196, IRGC102538 and IRGC102557) were highly resistant. M. graminicola significantly affected plant growth parameters in susceptible genotypes compared to resistant O. glaberrima accessions. The results were supported by histopathological studies that showed apparent giant cell formation in PR121 while penetration and development of M. graminicola juveniles were low in the O. glaberrima acc. IRGC102196. In silico analysis indicated that none of the reported nematode resistance genes from different crops had homology with the rice genome. The two anti-nematode genes (Oryzacystatin-I and Oryzacystatin-II) from O. sativa japonica revealed homology with O. sativa cv. PR121 and O. glaberrima acc. IRGC102206. Comparative analysis of these genes between PR121 and O. glaberrima acc. IRGC102206 resulted in the identification of SNPs/InDels that could be associated with nematode resistance. The identified SNPs/InDels could be validated, and further molecular studies are needed to provide insights into the resistance mechanism against rice RKN.