An RNA-seq dataset of 68-day-old lambs from two sheep breeds was analysed to identify differentially expressed genes involved in biological processes, molecular functions, cellular components, and pathways associated with resistance against Haemonchus contortus. Naïve Santa Ines (resistant breed) and Ile de France (susceptible breed) suckling lambs were serially infected with increasing numbers of H. contortus infective larvae (5400 in total) and had their abomasal mucosa sampled for sequencing. Gene Ontology annotation and enrichment analysis generated a list of 312 biological processes, 56 cellular components, and 106 molecular functions significantly enriched terms. Santa Ines lambs had significantly higher expression of genes involved in inflammatory responses, B-cell activation and receptor signalling pathways, complement activation, and angiogenesis. Most of the cellular components were associated with B-cell receptor complex, Fc-epsilon receptor I complex, and MHC class II protein (MHCII) complex terms. Additionally, most of the molecular functions were associated with IgE binding and receptor activity, IgA and immunoglobulin receptor binding. Santa Ines lambs showed a robust tissue repair mechanism, mediated mainly by fibroblast proliferation and collagen biosynthesis, epithelial cell maturation and structure maintenance, and strong smooth muscle contraction. Here, we present a detailed picture of the biological processes, and a comprehensive understanding of the gene architecture involved in the resistance trait of young lambs against H. contortus. The cluster of genes reported here might be useful for identifying target-based markers that could provide early selection of resistant sheep to H. contortus infection.