A hydrogeologic conceptual model that improves understanding of variability in aquitard integrity is presented for a fractured sedimentary bedrock unit in the Cambrian-Ordovician aquifer system of midcontinent North America. The model is derived from multiple studies on the siliciclastic St. Lawrence Formation and adjacent strata across a range of scales and geologic conditions. These studies employed multidisciplinary techniques including borehole flowmeter logging, high-resolution depth-discrete multilevel well monitoring, fracture stratigraphy, fluorescent dye tracing, and three-dimensional (3D) distribution of anthropogenic tracers regionally. The paper documents a bulk aquitard that is highly anisotropic because of poor connectivity of vertical fractures across matrix with low permeability, but with ubiquitous bed parallel partings. The partings provide high bulk horizontal hydraulic conductivity, analogous to aquifers in the system, while multiple preferential termination horizons of vertical fractures serve as discrete low vertical hydraulic conductivity intervals inhibiting vertical flow. The aquitard has substantial variability in its ability to protect underlying groundwater from contamination. Across widespread areas where the aquitard is deeply buried by younger bedrock, preferential termination horizons provide for high aquitard integrity (i.e. protection). Protection is diminished close to incised valleys where stress release and weathering has enhanced secondary pore development, including better connection of fractures across these horizons. These conditions, along with higher hydraulic head gradients in the same areas and more complex 3D flow where the aquitard is variably incised, allow for more substantial transport to deeper aquifers. The conceptual model likely applies to other fractured sedimentary bedrock aquitards within and outside of this region.