Although much progress has been made towards understanding the ripening of non-climacteric fruit using the strawberry as a model plant, the defined molecular mechanisms remain unclear. Here, RNA-sequencing was performed using four cDNA libraries around the onset of ripening, and a total of 31,793 unigenes and 335 pathways were annotated including the top five pathways, which were involved in ribosome, spliceosome, protein processing, plant-pathogen interaction and plant hormone signaling, and the important DEGs related to ripening were annotated to be mainly involved in protein translation and processing, sugar metabolism, energy metabolism, phytohormones, antioxidation, pigment and softening, especially finding a decreased trend of oxidative phosphorylation during red-coloring. VIGS-mediated downregulation of the pyruvate dehydrogenase gene PDHE1α, a key gene for glycolysis-derived oxidative phosphorylation, could inhibit respiration and ATP biosynthesis, whilst promote the accumulation of sugar, ABA, ETH, and PA, ultimately accelerating the ripening. In conclusion, our results demonstrate that a set of metabolism transition occurred during green-to-white-to-red stages that are coupled with more-to-less DEGs, and the oxidative phosphorylation plays an important role in the regulation of ripening. On the basis of our results, we discuss an oxidative phosphorylation-based model underlying strawberry fruit ripening.