This paper presents the first effort to unravel and quantify the strengthening of a shale induced by nanoparticle injection from the perspectives of cross-scale and multi-constituent mechanical properties. After being subject to injection of pure water and an aqueous suspension of carbon black nanoparticle of ~ 50 nm in diameter under a differential pressure of 850 kPa, the shale specimens were characterized by big data nanoindentation (BDNi) to probe the mechanical properties of both individual constituents at the microscale and the bulk rock at the macroscale, leading to comparatively assessing the effects of injecting pure water and aqueous nanoparticle suspension on the mechanical properties. Microstructural characterization by electron microscopy and X-ray computed tomography validates the successful injection of nanoparticles into the microcracks and micropores of the rock. While the nanoparticles can infiltrate to depths of up to 100 s μm in zones with densely populated microcracks, the maximum depths of injection in crack-free zones are only 2–5 μm. Moreover, the injected nanoparticles mostly act as inert fillers in the interconnected micropores and microcracks but can seldom enter the isolated micropores. Comparison of the BDNi results from pure water versus nanoparticle-injected specimens shows that the Young’s modulus of the clay matrix experiences the highest increase by 23.1%, while the counterpart of non-porous quartz the lowest by 12.8%. Overall, the bulk shale’s Young’s modulus increases by 21.5%. Such data are consistent with the microcharacterization results that the injected nanoparticles mainly remain in the micropores and microcracks within the clay matrix. Owing to their hydrophobic nature, the carbon black nanoparticles have little effect on the rock’s hardness. The findings can shed light on the practical applications of nanoparticle injection for improved wellbore stability in shale formations.