Abstract: Understanding the mechanical behavior and failure characteristics of anisotropic sedimentary rocks under true-triaxial in-situ stress conditions is critical in understanding and mitigating damaging formation slippage in subsurface reservoirs and containment structures. In particular, threshold conditions where structure dominates over intact failure remain undefined. By conducting systematic true-triaxial compression tests, we followed the evolution of deformation and failure in sedimentary rocks across a documented spectrum of lithological and structural characteristics in order to quantify and then classify this cross-impact. The failure features were characterized using acoustic emission (AE) monitoring, optical imaging, X-ray CT scans, and thin-section analysis. We characterized structural and deformational anisotropies in order to define the risk of structurally controlled slip failure. We identified three deformational and failure modes dominated by (I) purely stress-controlled failure, (II) mixed stress–structure-controlled failure, and (III) purely structurally controlled failure. As structural overprinting increased, failure mechanisms were found to shift progressively from Type I to III, thereby progressively capturing inherent rock anisotropy and complex fabric as well as ductile failure. This transition was characterized in terms of two parameters that alternately characterize structural (α) and deformational anisotropies (β) of rocks with these related to key visual, mechanical, and acoustic (AE) indicators. The greater the α (α > 2), the higher the β (β > 0), the more likely the transition from brittle failure to structurally controlled ductile shear reactivation along the bedding.