During CO2 injection in shale oil, CO2–crude oil interactions promote the precipitation of heavy organic fractions, which in turn alters the reservoir wettability. In this work, CO2 huff-n-puff tests were designed and performed in combination with contact angle measurements and one-/two-dimensional nuclear magnetic resonance (NMR) spectroscopy to investigate the multiscale effects of organic precipitation on reservoir wettability. A pore-scale water-wetness index was established using 1D NMR T2 spectra to quantitatively characterize the microscopic wettability evolution across various pore-size ranges. The mechanisms underlying wettability alteration were elucidated by analyzing changes in crude oil composition, shale surface morphology, and pore structure before and after CO2 exposure. Results indicate that the overall water-wetness of the reservoir is markedly weakened after CO2 huff-n-puff. Both macroscopic and microscopic wettability alterations exhibit consistent trends, evolving from strongly water-wet toward intermediate-wet and ultimately weakly oil-wet states as injection pressure, temperature, and soaking duration increase. Across various pore-size ranges, the reduction in water-wetness follows the order: micropores > small pores > mesopores > macropores. Notably, changes in the wettability of small pores have the strongest impact on the overall core wettability. The alteration of reservoir wettability is mainly governed by the precipitation of heavy organic fractions, together with modifications in surface roughness and pore structure. Correlation analysis reveals strong relationships between the precipitation ratios of resins and asphaltenes and the contact angle, with corresponding correlation coefficients of 0.8284 and 0.9328, respectively, highlighting that asphaltene precipitation has a more pronounced impact on wettability alteration. Moreover, organic precipitation increases surface roughness and decreases pore space, further diminishing water-wetness. Strong correlations are observed between contact angle and core-surface roughness, as quantified by arithmetic mean roughness (Ra) and root-mean-square roughness (Rq), yielding correlation coefficients of 0.8942 and 0.9116, respectively. Meanwhile, the correlation coefficient between pore volume variation and the pore-scale water-wetness index reaches 0.9503, highlighting that pore structure alteration plays a vital role in wettability evolution. This study elucidates the multiscale mechanisms by which organic precipitation controls wettability alteration, offering fundamental insights into enhanced oil recovery and the secure long-term storage of CO2 within shale formations.