Garole sheep exhibits within-breed difference in resistance to natural gastrointestinal nematode infection predominated by Haemonchus contortus. In the present study, interferon gamma gene (IFN-γ) was characterized in relation to parasitological, haematological, and immune response against H. contortus in resistant and susceptible Garole sheep. Resistant and susceptible Garole sheep were selected from the field based on consistent low faecal egg counts (FEC) for one year and single nucleotide polymorphisms (SNPs) in the IFN-γ gene. The partial amplification of IFN-γ gene (1282bp) revealed 4 SNPs exclusively in resistant sheep and 3 SNPs were shared between resistant and susceptible Garole sheep. The selected resistant and susceptible Garole sheep were challenged with H. contortus infection. The parasitological, haematological, immunological responses, and expression of IFN-γ gene were compared between the resistant and susceptible Garole sheep. The FEC of resistant sheep was significantly (P < 0.05) lower than the susceptible sheep infected with H. contortus. There was spontaneous elimination of H. contortus from 28 to 33days post infection (DPI) in resistant sheep. Haemoglobin and packed cell volume were significantly (P < 0.05) higher in resistant sheep than the susceptible sheep. The serum concentration of immunoglobulin (Ig)G1 and IgA and cytokine IFN-γ activity and also the expression of IFN-γ gene were significantly (P < 0.05) higher in the infected resistant sheep from 14 to 28 DPI compared to the susceptible sheep. In resistant sheep, IgA and IgG1 and cytokine IFN-γ positively correlated with expression of IFN-γ gene, and the SNPs recorded in the resistant sheep only might play an important role in conferring resistance against H. contortus. Further studies are required to elucidate the role of IFN-γ gene in H. contortus resistance in Garole sheep.