Addressing the linkages between global climate change, modification of surficial process dynamics, and subsequent tectonic responses requires integrated studies of orogenic and sedimentary systems in areas where specific end-members of the problem are encountered. The Gulf of Alaska borders the St. Elias orogen of Alaska and Canada, the highest coastal mountain range on Earth and the highest range in North America. This orogen is <30 m.y. in age, and mountain building occurred throughout a period of significant global climate change. This situation allowed Integrated Ocean Drilling Program Expedition 341 to examine the response of an orogenic system to the climatically driven establishment of a highly erosive glacial system. Additionally, the implications of Neogene glacial growth in the circum-North Pacific reach beyond the issue of tectonic response to increased glacial erosion and exhumation. As climate conditions determine the timing and patterns of precipitation, they control glacial dynamics, erosion, and sediment/meltwater and chemical fluxes to the ocean. A cross-margin transect was drilled during Expedition 341 to investigate the northeast Pacific continental margin sedimentary record formed during orogenesis within a time of significant global climatic deterioration in the Pliocene–Pleistocene that led to the development of the most aggressive erosion agent on the planet, a temperate glacial system. A remarkable expedition discovery is the substantial sediment volume accumulating on the shelf, slope, and deep sea fan since the early Pleistocene intensification of Northern Hemisphere glaciation and more significantly since the mid-Pleistocene transition. An exceptional shipboard paleomagnetic chronology and a biosiliceous and calcareous biostratigraphy provide a temporal framework to guide future analyses of particular glacial–interglacial periods.