<p>CO₂ hydrogenation, especially to methanol, is crucial to establishing sustainable closed-loop systems for carbon utilization. However, the difficulties of CO₂ activation at low temperatures and the ambiguity of structure–activity correlations are obstacles to reducing the energy consumption of the hydrogenation process. Here we report that molecularly defined Anderson PtMo₆O₂₄ clusters, sited within a robust metal–organic framework, are catalytic for low-temperature CO₂ hydrogenation. The performance of the cluster showed no signs of decay in either its activity or methanol selectivity over 3,600 h at 180 °C. It also achieves a per-pass yield exceeding that of state-of-the-art heterogeneous catalysts under similar conditions. Combined in situ spectroscopy and density functional theory calculations demonstrated that CH₃OH formation is dominated by the reverse water–gas shift and subsequent CO* hydrogenation pathway, while the HCOO* pathway may serve as a supplementary route. The well-defined cluster structure offers an ideal model for elucidating structure–activity correlations and opens exciting avenues for the rational design of high-activity, low-temperature catalysts for CO₂ hydrogenation.</p><p></p>