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Abstract Physico-mechanical properties of shale are important parameters in evaluating the stability of potential wellbore and the design of hydraulic fracturing, which are primarily affected by their non-uniform spatial distribution of the microscopic physical–mechanical properties at particle scale. A series of constant strain rate experiments and stress-cycling experiments on shale specimens with different bedding dip angles were conducted to have a comprehensive understanding of the effect of the non-uniform distribution of microscopic failure stress on macroscopic physico-mechanical properties. According to the experimental results and Weibull distribution, we find that bedding dip angle and the dynamic load applying type affect the spatial distributions of microscopic failure stress. The values of crack damage stress (σ cd), σ cd/σ ucs (peak stress), ε cd (strain at crack damage stress), Poissons' ratio (ν), elastic strain energy (U e) and dissipated energy (U irr) of the specimens with more uniform distribution of microscopic failure stress are overall higher, while ε ucs (peak strain)/ε cd and elastic modulus (E) are lower. The dynamic load enables the spatial distributions of microscopic failure stress trend to be more homogeneous prior to the final failure with the increment of σ cd/σ ucs, ν, U e and U irr and the decrement of E.