Pore systems in the Middle Permian Phosphoria Rock Complex (PRC), Rocky Mountain Region, USA, evolved with biotic and chemical dynamics in a shallow epicontinental seaway undergoing extreme environmental shifts. Biochemical responses to environmental changes directly affected pore systems and controlled diagenetic pathways through burial. Petrographic methods and spatially resolved measurements of δ 18 O in sequence stratigraphic context allow characterization of pore systems and their evolution in heterogenous biochemical sediments. Pore systems vary regionally and across systems tracts on second-order (9–10 million years [MY]) and third-order (2–5 MY) timescales. Minimal porosity occurs in transgressive mudrocks rich in organic matter (OM), phosphorites, and carbonates. Cool, acidic, low-oxygen, nutrient-rich basinal waters interacted with warm open to restricted shelfal waters in transgressions. This resulted in accumulation and microbial decay of S-rich OM, phosphatization, carbonate precipitation, silicification, as well as deposition of calcitic-biotic debris (bryozoans, brachiopods, and crinoids) and micrite. Relative to landward and highstand marine components, transgressive basinal marine carbonates and silica are δ 18 O depleted due to microbial decay of OM. Extensive cementation coupled with near-surface compaction and recrystallization of micrite occluded large portions of porosity in transgressive phosphorites and carbonates. Porosity in these rocks is dominated by interparticle and, to a lesser degree, intraparticle microporosity in microbored phosphatized and micritized grains. Phosphorites are compacted where cements are not pervasive. OM-rich sediments host minimal volumes of interparticle nanoporosity due to mechanical compaction and incursion of secondary OM (bitumen) during burial. PRC OM is S-rich, due to sulfate-reducing bacterial enrichment, and locally abundant. This drove early generation of secondary OM and inhibited OM-hosted porosity development through thermal maturation. Large volumes of porosity accumulated in highstand sediments and varied with transitions from silicisponge spicule cherts and calcitic-biota carbonates to pervasively dolomitized micritic, peloidal, aragonitic mollusk, and peritidal microbial sediments. These biochemical transitions, and ultimately pore-system evolution, were driven by interaction between oxygenated open marine waters, eolian siliciclastic debris, and increasingly restricted shelfal waters. Marine carbonate and silica δ 18 O are consistent with Middle Permian open marine waters but are enriched landward and through highstands with evaporative fractionation. This δ 18 O-enriched authigenic silica in carbonates and evaporite replacements, as well as δ 18 O enrichment through silica precipitation, suggest dolomitization and silicification were driven by evaporitic processes. In spiculitic cherts and siltstones, silicification and carbonate diagenesis resulted in small volumes of intraparticle, interparticle, and moldic porosity, as well as increased susceptibility to fracturing and associated permeability enhancement. Chalcedony in spiculites and silicified carbonates host minor volumes of porosity where moganite crystallites dissolved during hydrocarbon migration. Highstand dolomites host abundant intercrystalline, moldic, fenestral, and interparticle macroporosity and microporosity, especially in peloidal wackestones, mollusk debris, ooid grainstones, and peritidal microbialites. Dolomitization resulted in dissolution of aragonitic mollusk and ooids, cementation, and preservation of primary porosity. Porosity loss through burial in dolomites occurs through mechanical compaction, and to a lesser degree, precipitation of zoned carbonate cements that are δ 18 O depleted relative to earlier dolomite. Compaction strongly decreases intercrystalline porosity in dolomitized peloidal wackestones. Secondary OM related to hydrocarbon migration coats surfaces and fills small pore volumes, inhibiting burial cementation.