Water infiltration into fractures is ubiquitous in crustal rocks. However, little is known about how such a progressive wetting process affects fracture stiffness and seismic wave propagation, which are highly relevant for characterizing fracture systems in situ. We study the acousto‐mechanical behavior of a free‐standing fractured granite subjected to gradual water infiltration with a downward‐moving wetting front over 12 days. We observe significant differences (i.e., by an order of magnitude) in wave amplitudes across the fractured granite compared to an intact granite, with both cases showing a strong correlation between wave amplitudes and wetting front movement. Effects of water infiltration into the fracture and surrounding matrix on seismic attenuation are captured by a numerical model with parameters constrained by experimental data. Back‐calculated fracture stiffness decreases exponentially with the wetting front migration along the fracture. We propose that moisture‐induced matrix expansion around the fracture increases asperity mismatch, leading to reduced fracture stiffness.