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Argon gas and liquid (dodecane) permeability measurements in two mixed quality siliceous mudstone samples within the Wolfcamp formation demonstrate that it is possible to close multiple bedding parallel open artificial micro-fractures and obtain representative matrix permeability by applying two confining stress cycles at a constant pore pressure under effective stresses ranging from 6.9 MPa to 59.7 MPa. The clearly micro-fractured sample exhibited a three-order decrease in permeability from 4.4 × 10−17 m2 to 2.1 × 10−20 m2. In contrast, the relatively intact sample exhibited initial liquid permeability of 1.6 × 10−19 m2 that declined gradually with stress to 3.0 × 10−20 m2. In this study, we developed a new permeability testing protocol and analytical approaches to interpret the evolution of micro-fractures and estimate the matrix permeability based on initial pulse-decay gas permeability measurements. The insights gained are useful to identify pore-scale controls on fluid flow behavior using SEM petrography and pore-space characterization and validate fundamental fluid flow mechanisms examined using pore-scale numerical models.