The limited mechanistic understanding and ambiguous structure–performance relationships have hindered the optimization of Cu-based catalysts for the reverse water–gas shift (rWGS) reaction. Here, we report a flame spray pyrolysis (FSP)-derived Cu–CeO2 catalyst featuring highly dispersed, surface-substituted Cu+ species (CuyCe1–yO2–x) anchored on a defect-rich ceria matrix. This catalyst demonstrates excellent stability and outstanding rWGS activity at 600 °C, achieving a CO production rate of 8094 mmol/gcat./h, surpassing the conventional Cu–CeO2 catalyst and other reported rWGS catalysts. In situ spectroscopic analyses, supported by DFT calculations, reveal three parallel reaction pathways in which carboxylate- and formate-mediated routes proceed at distinct active sites. A clear structure–activity correlation is established across Cu+, Cu0, and ceria defect sites in the FSP-derived catalysts. Notably, a previously underexplored carboxylate-mediated pathway, facilitated on the surface-substituted Cu+ structure, is identified as the dominant route, featuring a significantly lower apparent activation energy (20–30 kJ/mol) compared to the classical formate pathway.