Plant systemic acquired resistance (SAR) is a phenomenon whereby the recognition of a local microbial invasion in aerial tissue confers a ‘whole-plant’ immune response against a wide range of pathogens. For the model plant Arabidopsis thaliana and various other angiosperms, the key metabolites Pipecolic acid (Pip) and N-hydroxylated pipecolic acid (NHP), synthesized by the reductase SAR-Deficient 4 (AtSARD4) and Flavin-monooxygenase 1 (AtFMO1), respectively, are crucial for proper SAR establishment. However, the extent to which NHP biosynthesis contributes to SAR in common hexaploid wheat (Triticum aestivum) remains unclear. Here, we utilized a combination of protein homology, phylogenetic and transcriptomic analyses to elucidate functional orthologs of AtSARD4 and AtFMO1 in wheat. 48 TaFMO1-like and three TaSARD4 candidates were identified, from which representatives were selected for further functional characterization. All three TaSARD4-expressing transgenic Atsard4 Arabidopsis lines generated displayed dwarfism characteristic of autoimmunity, with significant reductions in rosette size (>45%) compared to the Atsard4 deletion mutant. Two TaFMO1-expressing transgenic Atfmo1 Arabidopsis lines revealed a partial recovery in SAR when infected by the oomycete Hyaloperonospora arabidopsidis, indicating possible functional complementation. Furthermore, supplementing 10mM NHP to a local wheat leaf significantly and systemically reduced by 3-fold the proliferation of the biotrophic wheat fungal pathogen, Puccinia triticina (Pt); the quantification of basal and Pt-induced NHP and Pip levels in wheat by HPLC-MS is currently underway. Altogether, our results implicate that the NHP biosynthetic pathway is conserved for pathogen defense in wheat and underscores the need for comprehensive strategies when attempting to assimilate knowledge from model to non-model crop systems.