In the eastern Anadarko Basin of central Oklahoma, the variability of Mississippian lithofacies, diagenetic products, and reservoir quality are critical for reservoir development. We investigated lithofacies variability based on sedimentological characteristics and diagenetic alteration through integration of core and thin sections by using optical microscope, scanning electron microscope (SEM), energy dispersive x-ray diffraction spectroscope (EDX), and electron probe micro-analyzer (EPMA)-cathodoluminescence (CL) analyses. Based on detailed descriptions of 5 cores (~260 m; ~850 ft) and analysis of 34 thin sections, we concluded the Mississippian strata consists of 8 lithofacies that represent wave-influenced nearshore with restricted embayment (lagoon) and channel or lobe deposits. We observed diagenetic alteration including calcite cementation, mechanical compaction, albitization, quartz cementation, silicification, dolomitization, Fe-dolomite cementation, pyritization, and dissolution. A paragenesis scheme suggests that quartz cementation occurred earlier compared to albitization and Fe-dolomite cementation. The Fe-dolomite is the latest authigenic mineral formed whereas the quartz and calcite cement can be attributed to earlier diagenesis. The calcite, quartz, and Fe-dolomite cementation might have potentially increased the brittleness index and frackability of the rocks. Reservoir quality is relatively good in the channel or lobe deposits and is generally poor in the upper shoreface to upper offshore environments. The reservoir quality is significantly reduced by clays, calcite cement, and mechanical compaction. However, the dissolution of calcite cement and detrital grains tends to improve reservoir quality by forming secondary pores. This study proves that understanding the characteristic of lithofacies variation, depositional environments, and diagenetic alterations of the Mississippian strata is crucial for optimal development of the Mississippian reservoirs in the eastern Anadarko Basin. It provides a predictive framework that aids in reservoir characterization.