<p>Compared to the sluggish kinetics observed in methanol-mediated side-chain alkylation of methyl groups with sp³ C–H bonds, CO₂ hydrogenation emerges as a sustainable alternative strategy, yet it remains a challenge. Here, as far as we know, it is first reported that using CO₂ hydrogenation replacing methanol can conduct the side-chain alkylation of 4-methylpyridine (MEPY) over a binary metal oxide-zeolite Zn₄₀Zr₆₀O/CsX tandem catalyst (ZZO/CsX). This ZZO/CsX catalyst can achieve 19.6% MEPY single-pass conversion and 82% 4-ethylpyridine (ETPY) selectivity by using CO₂ hydrogenation, which is 6.5 times more active than methanol as an alkylation agent. The excellent catalytic performance is realized on the basis of the dual functions of the tandem catalyst: hydrogenation of CO₂ on the ZZO and activation of sp³ C–H bond and C–C bond coupling on the CsX zeolite. The thermodynamic and kinetic coupling between the tandem reactions enables the highly efficient CO₂ hydrogenation and C–C bond coupling. In-situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and density functional theory (DFT) calculations suggest that the CH_xO* (CH₂O*) species, rather than methanol produced from CO₂ hydrogenation, is the key intermediate to achieve the C–C bond coupling.</p>