The Guanajuato Mining District of central Mexico is one of the main silver and gold deposits in the world. It is in the State of Guanajuato in the southern part of the Sierra Madre Occidental (SMO) volcanic province. The mining district developed within a mid-Tertiary volcano-sedimentary sequence that includes thick alluvial-fan deposits accumulated in a tectonic basin during the Eocene-Oligocene named the Guanajuato Red Conglomerate and an overlying volcanic sequence mostly pyroclastic of Oligocene age. The mid-Tertiary stratigraphy of Guanajuato is revised and reinterpreted in the light of new fieldwork and U-Pb ages, which document a close timing between all units of the volcanic succession at the top of the Guanajuato Red Conglomerate. This sequence is made of pyroclastic density current deposits formed during episodic events from the Guanajuato caldera. A new nomenclature of the caldera’s units is proposed; the Guanajuato Caldera Volcanic Group, which includes the Guanajuato Pyroclastic Formation represented by the Loseros PDC deposits and the Bufa-Calderones ignimbrites emplaced around 32.8 ± 0.2 Ma, and the post-collapse lava domes of El Rodeo and Chichíndaro formations emplaced at 31–30 Ma. Apparently, a resurgent pulse of the caldera uplifted the collapsed intra-caldera blocks, so that the caldera floor is now exposed. The caldera collapse was controlled by the pre-existing normal faults inherited from the previous tectonic basin; thus, it is classified as a graben-type caldera, with a square shape and a size of 15 × 16 km. By comparison with other similar calderas of Mexico, the Guanajuato caldera is another case study of graben-type calderas of the SMO coinciding with mineral districts, such as Bolaños (Jalisco).