To clarify the regulatory laws of the fines content (FC) and particle size ratio (SR) on the mechanical properties of sand–fines mixtures and reveal the underlying microscopic mechanical mechanisms, this study takes sand–fines mixtures composed of natural river sand and silt as the research object. It systematically investigates the macro-mechanical behaviors and micro-interaction mechanisms of the mixtures by combining laboratory triaxial tests and discrete element method (DEM) simulations. First, through conducting triaxial drained shear tests on mixtures with three particle size ratios (SR = 9.1, 18.7, and 39.7) under seven fines contents (FC = 0%, 10%, 20%, 30%, 50%, 70%, and 100%), it is found that both the peak friction angle (φ_ps) and critical-state friction angle (φ_cs) of sand–fines mixtures show a “first increase, then decrease” trend with the increase in FC. The peak inflection points of their variation curves are the threshold fines content related to SR; meanwhile, a fines content below this threshold has an inhibitory effect on dilatancy, while that above this threshold exerts a promotive effect on dilatancy. Subsequently, by exploring the microscopic contact behaviors of sand–fines mixtures, it is observed that, under the fines content corresponding to the highest peak strength, the strong contact network and weak contact network inside the material form an optimal coordination between efficient load-bearing and stable support. This coordination enables the macro-strength of the mixture to reach the peak at this fines content. In addition, by modifying the weight coefficient of fabric anisotropy, a unique linear relationship between the fabric anisotropy of strong contacts and the stress ratio can be established, confirming that the strong contact network plays a core mechanical role in mixtures with different FC values.