Abstract This study reports new geochemical and Sr–Nd–Pb isotopic data for Miocene to Quaternary basaltic to andesitic, dacitic, and rhyolitic volcanic rocks from the Huichapan caldera, located in the central part of the Mexican Volcanic Belt (MVB). The initial Sr and Nd isotopic ratios, except for one rhyolite, range as follows: 87Sr/ 86Sr 0.70357–0.70498 and 143Nd/ 144Nd 0.51265–0.51282. The Sr–Nd–Pb isotopic ratios are generally similar to those for volcanic rocks from other areas of the central and eastern parts of the MVB. The isotopic ratios of one older pre-caldera rhyolite (HP30) from the Huichapan area, particularly its high 87Sr/ 86Sr, are significantly different from rhyolitic rocks from this and other areas of the MVB, but are isotopically similar to some felsic rocks from the neighbouring geological province of Sierra Madre Occidental (SMO), implying an origin as a partial melt of the underlying crust. The evolved andesitic to rhyolitic magmas could have originated from a basaltic magma through a combined assimilation and fractional crystallisation (AFC) process. Different compositions, representing lower crust (LC) and upper crust (UC) as well as a hypothetical crust similar to the source of high 87Sr/ 86Sr rhyolite HP30, were tested as plausible assimilants for the AFC process. The results show that the UC represented by granitic rocks from a nearby Los Humeros area or by Cretaceous limestone (L) rocks outcropping in the northern part of the study area, and the LC represented by granulitic xenoliths from a nearby San Luis Potosı́ (SLP) area are not possible assimilants for Huichapan magmas, whereas a hypothetical crust (HA) similar in isotopic compositions to rhyolite HP30 could be considered a possible assimilant for the AFC process. Chemical composition of assimilant HA, although not well constrained at present, was inferred under the assumption that HP30 type partial melts could be generated from its partial melting. These data were then used to evaluate the proposed AFC process to explain the evolution of the Huichapan magmas.