This detailed macroseismic study of a locally devastating earthquake doublet in the western part of the Trans‐Mexican volcanic belt, north of Fuego de Colima Volcano, on 22 and 23 October 1749 is based on contemporary documentary sources. The shocks razed the towns of Zapotlán el Grande (now Ciudad Guzmán) and Sayula and caused major damage in Amacueca and Atoyac. A first mainshock on 22 October 1749 at 4 p.m. was devastating in Sayula and Zapotlán el Grande and caused some damage in Amacueca. A stronger second mainshock later, on 23 October 1749 at about noon, was destructive in Sayula, Amacueca, and Zapotlán el Grande where only three residential buildings remained standing. Estimates of the intensity magnitude of the mainshocks range between 5.7 and 6.0, with a preferred magnitude of 5.8. The macroseismic intensity distribution, limited area of destruction, and prolonged sequence of aftershocks, lasting at least until August 1750, indicate a local earthquake source in the northern Colima graben, most likely on the major fault bounding the Sayula half‐graben in the west.