The use of mineral diagenetic indices and organic matter maturity is useful for reconstructing the evolution of sedimentary basins and critical assessments for potential source rocks for petroleum exploration. In this study, the relationship of clay mineral diagenesis and organic matter thermal indices (Rock-Eval Tmax) and calculated vitrinite reflectance (%Ro) were used to constrain the maximum burial depths and temperatures of three distinct intervals within the northern Permian Basin, USA. X-ray diffraction of clay fractions (<2 µm) consists of illite, chlorite, and illite-smectite intermediates. Primary clay mineral diagenetic changes progressively increase in ordering from R0 to R1 I-S between 2359.5 and 2485.9 m and the appearance of chlorite at 2338.7 m. Rock-Eval pyrolysis data show 0 to 14 wt% TOC, HI values of 40 to 520 mgHC/g TOC, and S2 values of 0 to 62 mg HC/g, with primarily type II kerogen with calculated %Ro within the early to peak oil maturation window. Evaluation of the potential for oil generation is relatively good throughout the Tonya 401 and JP Chilton wells. Organic maturation indices (Tmax, %Ro) and peak burial temperatures correlate well with clay mineral diagenesis (R0–R1 I-S), indicating that maximum burial depths and temperatures were between 2.5 and 4 km and <100 °C and 140 °C, respectively. Additionally, the use of clay mineral-derived temperatures provides insight into discrepancies between several calculated %Ro equations and thus should be further investigated for use in the Permian Basin. Accordingly, these findings show that clay mineral diagenesis, combined with other paleothermal proxies, can considerably improve the understanding of the complex burial history of the Permian Basin in the context of the evolution of the southern margin of Laurentia.