Understanding and simulating the evolution of fracture in cellulose-based paper materials is vital for many eco-sustainable applications of packaging solutions. In this work, we conduct an integrated experimental-statistical mechanics analysis to elucidate how the microstructural mechanisms govern the fracture behavior of paper. We employ in-situ tensile tests combined with confocal microscopy to observe and analyze key microstructural phenomena, such as fibers’ activation and recruitment, and progressive tensile failure of unnotched paper samples under uniaxal loading. The developed stochastic mechanics critical cross-section model to treat the cellulose fiber network is able to decouple the stochastic morphological parameters from the constitutive model of the fibers. Notably, it robustly predicts the anisotropic properties of paper materials in the machine direction (MD) and cross-machine direction (CD) as a direct consequence of the different statistical distribution of fibers’ orientation, for the same fiber constitutive model. The proposed approach is finally employed to get an insight into the role of the main morphological parameters, local/non-local fibers’ strain redistribution, and finite elasticity of fibers on the whole mechanical behavior of paper.