Due to extensive glacial cover, the evolution or the West Antarctic Rift System (WARS) and the proto-Pacific margin of Gondwana are still poorly understood. Here we present the first low-temperature thermochronology data from eastern Marie Byrd Land and the Pine Island Bay area. The goal of our study is to decipher the long-term thermotectonic evolution of this area, infer its denudation history, and to provide estimates for paleotopography and potential links to the glaciation history. Our data show that during early and mid-Cretaceous subduction along the proto-Pacific margin, all of Marie Byrd Land and the Pine Island Bay area experienced rapid exhumation. This rapid exhumation continued for about 25 Myr after subduction stopped, presumably driven by tectonic denudation related to continental breakup between Zealandia and West Antarctica and rifting activity of the WARS. This late Cretaceous extension period was related to rapid topography reduction, as expressed by the formation of the West Antarctic erosion surface close to sea level, and was probably related to free-boundary gravitational collapse of the Gondwanide orogen. By ~60 Ma, rapid exhumation stopped, which we interpret as cessation of the first WARS rifting period. Cretaceous rapid exhumation was followed by very low exhumation rates throughout the Cenozoic, which we explain by tectonic quiescence and subdued topography. After ~30 Ma, and restricted to the western Pine Island Bay area, rapid exhumation resumed, presumably coeval with large-scale crustal tilting of the eastern Pine Island Bay area towards the Pine Island trough. We interpret this as indicating renewed activity of the WARS, (i) suggesting that Cenozoic rifting activity was much more localized than Cretaceous rifting, and (ii) corroborating previous assumptions that the WARS branches from the continental interior into the Amundsen Sea. Our structural model, based on the thermochronology data, kinematically links the rift branches reaching into the Bellingshausen and Amundsen Seas with the Byrd Subglacial Basin and the Bentley Subglacial Trench, requiring dextral transtension for the Bellingshausen Sea area and sinistral transtension for the Amundsen Sea area. Furthermore, our data suggest that enhanced denudation along the flanks of the Marie Byrd Land dome – and thus presumably its uplift – only started at ~20 Ma, that is, nearly 10 Ma later than previously assumed. The Marie Byrd Land dome is the only extensive part of continental West Antarctica elevated above sea level. Since the formation of a continental ice sheet requires a significant area of emergent land, our data imply that initiation of extensive glaciation of this part of West Antarctica may only have started since the early Miocene.