The timing and source of deformation responsible for formation of the Sierra Madre de Chiapas (south Mexico) are unclear. To address this, apatite fission track and U-Th-He thermochronometry, combined with zircon U-Pb dating, were performed on bedrock and sedimentary samples of the Sierra Madre de Chiapas to discern timing of exhumation and identify sediment source areas. The U-Pb results show that Paleocene–Eocene terrigenous units outcropping at the northern section of the Sierra were mostly derived from Grenville (∼1 Ga) basement whereas the internal sections of the chain yield mainly Permian to Triassic ages (circa 270–230 Ma) typical of the Chiapas massif complex. Grenville-sourced sediments are most probably sourced by the Oaxacan block or the Guichicovi complex and were deposited to the north of the Sierra in a foreland setting related to a Laramide deformation front. Other possibly source areas may be related to metasedimentary units widely documented at the south Maya block such as the Baldi unit. The apatite fission track and U-Th-He data combined with previously published results record three main stages in exhumation history: (1) slow exhumation between 35 and 25 Ma affecting mainly the Chiapas massif complex; (2) fast exhumation between 16 and 9 Ma related to the onset of major strike-slip deformation affecting both the Chiapas massif complex and Chiapas fold-and-thrust belt; and (3) a 6 to 5 Ma period of rapid cooling that affected the Chiapas fold-and-thrust belt, coincident with the landward migration of the Caribbean–North America plate boundaries. These data suggest that most of the topographic growth of the Sierra Madre de Chiapas took place in the middle to late Miocene. The new thermochronological evidence combined with stratigraphic and kinematic information suggests that the left-lateral strike-slip faults bounding the Chiapas fold-and-thrust belt to the west may have accommodated most of the displacement between the North American and Caribbean plates during the last 6–5 Ma.