The Gutenberg–Richter law and the fragment asperity model have been used in different active volcanoes or geothermal zones to analyze the manner in which seismicity evolves in these environments. Different volcanoes exhibit different behavior on their seismicity statistical features. Seismicity variations have been associated with changes in the state of stress, or with heterogeneity in material properties. Quantifying and interpreting the seismicity reported at currently active Colima volcano has been challenging, even though it is of critical importance for evaluating the hazard it poses to the nearby population centers. In this work, the frequency-magnitude distribution was spatially mapped beneath the Colima Volcano in Western Mexico using an earthquake catalog of 1192 relocated events that occurred during March 1998–December 1999, April–July 2005, and October–December 2009. Zones of high seismic b-values (> 3.0) are found at depths of 0 to 2.1 km a.s.l. below the crater. The anomalies are statistically significant based on Utsu's p-test. We found evidence to relate high b-value anomalies with the movement of magmatic fluids and/or high rock heterogeneity due to the local stress regime. Stress inversion results showed that the seismicity reflects an extensional stress regime. Our interpretation is supported by structural geology information. Orientation of the principal axes is consistent with the E-W-trending fault system at the Colima Volcanic Complex. Using the fragment asperity model, we found that a q-value of 1.21 is able to model the relocated frequency size distribution. The calculated q-values at Colima volcano and other volcanic zones (Yellowstone Park volcanic field, El Hierro, and Santorini volcanoes) exhibit a lower numerical value (0.5 < q < 1.6) than those reported as representative average values in different geological environments (q = 1.6–1.7). We discovered that q-values in volcanic regions are lower than typical values reported worldwide. We infer that the q-values at Colima Volcano are related to areas of increased crack density, high pore pressure, or both, related to the presence of nearby magma bodies.