The boundary between the Sierra Madre Occidental (SMO) and the Trans-Mexican Volcanic Belt (TMVB) is well exposed along the Santiago River, on the border of the states of Nayarit and Jalisco. This region includes a polydeformed belt produced by the relative motion between the Jalisco Block and the SMO, here defined as the “Rio Santiago Shear Zone” (RSSZ). In this work, we present detailed geological cartography, petrographic descriptions, and new zircon U-Pb ages that allow us to establish the stratigraphy of the region surrounding the RSSZ, providing temporal constraints to its tectonic evolution. In the mapped area, the base of the SMO stratigraphic column consists of a succession of massive andesitic lava flows intruded by felsic dikes and a felsic subvolcanic body of 27.5 and 27.2 Ma, and it is covered by a series of ignimbrites of 26.8 and 25.3 Ma. A red beds succession separates a second package of ignimbrites of ∼20-19 Ma, in turn capped by rhyolitic lava domes of 19.7 and 18.6 Ma and a rhyodacitic lava flows of 15.6 Ma, this Miocene succession is also intruded by a felsic body of 18.3 Ma west of the La Yesca dam. The SMO succession is covered by rocks belonging to the bimodal volcanism of the TMVB, emplaced between the end of the Miocene and the Pleistocene. The RSSZ developed through several deformation phases that occurred since the end of the Oligocene. The Oligocene succession of the SMO is affected by NE-SW and WNW-ESE trending lateral faults, NW-SE open folds and WNW-ESE and E-W trending reverse oblique faults. Some of the reverse oblique faults were later reactivated as normal faults. WNW-ESE trending normal faults associated with the Tepic-Zacoalco Rift affected the area south of the Santiago River during the Pliocene and Pleistocene. Normal faulting produced an accumulated vertical offset up to 700 m between the northern and southern regions of the Santiago River.