Resistance training (RT) is the gold standard intervention for ameliorating sarcopenia. Outstanding mechanistic questions remain regarding the malleability of the molecular determinants of skeletal muscle function in older age. Discovery of proteomics can expand such knowledge. We aimed to compare the effect of RT on the skeletal muscle proteome and neuromuscular function (NMF) in older and younger women. Seven young (22 ± 6 years) and eight older (63 ± 5 years) women completed 8 weeks' leg RT. Pre- and post-training, measures of leg and handgrip strength, NMF and vastus lateralis (VL) biopsies were obtained. Tandem-mass-tagged skeletal muscle proteomic analyses were performed. Data were analysed using differential expression and weighted gene co-expression network approaches. Proteins related to skeletal muscle contraction were lower in older skeletal muscle; this was not normalised by RT. Following RT, older women had higher expression of VL mitochondrial biogenesis proteins compared to the young, a reversal of pre-training observations. Seventy proteins were differentially expressed between age groups. VL expression of these proteins in older women was consistently and significantly associated with poorer leg strength/NMF. Conversely, VL expression of these proteins in older women was often associated with greater handgrip strength. This study has identified important differences in the molecular responses of young and old skeletal muscle to RT. We have demonstrated their close relationship with skeletal muscle function. Proteins that are refractory to RT may represent targets to ameliorate sarcopenia. We have described a 'proteomic-function' relationship that appears to be muscle-specific. Future research should further unpick these complex relationships.