This study investigates the origin of various diagenetic alteration products in Eocene, deeply buried volcaniclastic sandstones in the Huizhou depression, Pearl River Mouth Basin, China, to evaluate the influence of diagenesis on reservoir quality. Evidence from petrography and geochemistry of diagenetic minerals illustrates a relatively complicated diagenetic history in the volcaniclastic sandstones. Eogenetic hydration of volcanic glass materials led to precipitation of grain-coating chlorite and heulandite cements. First-generation laumontite cement (60°C–70°C) formed via heulandite transformation during eogenesis. Variable mesogenetic alteration products developed in an organic-CO2–based system and mainly included (1) precipitation of pore-filling chlorite, quartz, kaolinite, second-generation laumontite (90°C–100°C), and calcite cements (δ13CVPDB, −20.96‰ to −7.8‰; δ18OVPDB, −15.78‰ to −10.88‰); (2) dissolution of volcanic glass, orthoclase and laumontite; and (3) chloritization and albitization. Kinetic modeling results, coupled with petrographic observations, reveal that although total reservoir quality was not significantly enhanced by mesogenetic dissolution, diffusion of dissolved ions (e.g., Fe2+, Mg2+, and Ca2+) among different depositional microfacies produced a heterogeneous distribution of diagenetic alteration products and different reservoir evolutionary pathways. This diffusive transportation process led to local enhancement of reservoir quality in distributary-channel microfacies and local destruction of reservoir quality in mouth-bar and sheet-sand microfacies.