Oil and gas operations in sedimentary basins have revealed the occurrence of significant temperature anomalies at depth, raising the possibility of major geothermal resource potential in the sedimentary sequences. The efficient development of such a resource may require enhancement by hydraulic stimulation. However, effective stimulation relies on an initial assessment of in situ mechanical properties and a model of the rock response. Here, we examine the distribution of mechanical properties (unconfined compressive strength, UCS; ultrasonic velocity-derived Poisson ratio, ν; and, scratch toughness, Ks) along the cored interval of a sedimentary formation with a known low-to-medium temperature geothermal anomaly in the Permian Basin, U.S. Our results reveal the presence of mechanical stratigraphy along the core, demonstrated by the alternation of distinct soft–hard (i.e.,less stiff-to-stiff) mechanical zone couplets composed of: (1) mechanically softer 0.17-m-thick Zone-A and 0.18-m-thick Zone-C with mean values of UCS = 110 MPa, ν = 0.25, Ks = 1.89 MPa·√m; and (2) mechanically harder 0.41-m-thick Zone-B and 0.15-m-thick Zone-D which show mean values of UCS = 166 MPa, ν = 0.22, and Ks = 2.87 MPa·√m. Although X-ray diffraction analyses of the samples suggest that the entire rock matrix is dominated by dolomite, the harder zones show an abundance of quartz cement (> 30%) and relatively lower phyllosilicate mineral content (< 2%) than the softer zones. Further, we observe that the mechanically harder zones have the greatest occurrences and thicknesses of hydrothermal alterations (anhydrite veins and nodules), indicating that the rock had experienced hydrothermal fluid circulation (basinal brines) in the past. We infer that the mechanical stratigraphy most likely influenced the spatial clustering of fractures that facilitated hydrothermal fluid migration in the past, and provides insight that is relevant for the exploitation of geothermal energy resources in sedimentary basins. We suggest that the harder zones or formation intervals with higher ratios of the hard zones relative to soft zones represent viable targets for hydraulic stimulation of a sedimentary-hosted geothermal reservoir, both for the emplacement of new fractures and the linkage of pre-existing fractures to allow efficient fluid circulation. Our findings in this study provide insight that is relevant for understanding the complexity of pre-existing mechanical heterogeneity in sedimentary-hosted geothermal reservoir targets in other places.