This study elucidates the intricate molecular dynamics of the Stem-Physical-Strength-Mediated-Resistance (SPSMR) mechanism against Sclerotinia sclerotiorum in oilseed Brassica. This study explores how resistant and susceptible genotypes respond to S. sclerotiorum and their stem physical strength at various infection stages, revealing the molecular basis of SPSMR-mechanism. Statistically significant differences (P ≤ 0.05) were observed between genotypes over time, where the resistant genotype showed reduced stem lesion length, stem diameter, and stem water content, along with increased stem dry matter content, stem specific density, stem breaking force, stem breaking strength, and lignin content compared to the susceptible counterpart. Through gene expression analysis, the study unraveled unique patterns of differentially expressed genes linked to cell wall reinforcement, pathogenesis and disease resistance. Upregulation of genes associated with arabinogalactan protein, xyloglucan endotransglucosylase/hydrolase, pectinesterase, expansins, S-adenosylmethionine-dependent methyltransferase, wall-associated kinases, peroxidases, laccases and phenylalanine ammonia-lyase as well as other genes associated with lignin-biosynthesis was evident in the resistant genotype. Additionally, gene ontology and KEGG enrichment analyses highlights the synergy between stem physical strength and molecular components, revealing a distinctive defense strategy involving the coordinated upregulation of genes responsible for cell-wall strengthening, disease resistance, and pathogenesis-related proteins in the resistant genotype. Conversely, compromised expression patterns in the susceptible genotype underscore its challenge in mounting a robust defense. Strikingly, genes regulating intracellular pH homeostasis emerge as potential countermeasures against S. sclerotiorum virulence. Ultimately, these findings provide a new perspective on the molecular basis of the SPSMR mechanism in boosting host genetic resistance against S. sclerotiorum in oilseed Brassica and other hosts. However, future research is required to investigate diverse genotypes, additional pathways, and regulatory elements in order to achieve a comprehensive understanding of SPSMR in oilseed Brassica.