We present new isotopic and micropaleontological data from a depth transect on Shatsky Rise that record the response of the tropical Pacific to global biotic and oceanographic shifts during the mid-Maastrichtian. Results reveal a coupling between the upper ocean, characterized by a weak thermocline and low to intermediate productivity, and intermediate waters. During the earliest Maastrichtian, oxygen and neodymium isotope data suggest a significant contribution of relatively warm intermediate water from the North Pacific. Isotopic shifts through the early Maastrichtian suggest that this warmer water mass was gradually replaced by cooler waters originating in the Southern Ocean. Although the cooler water mass remained dominant through the remainder of the Maastrichtian, it was displaced intermittently at shallow intermediate depths by North Pacific intermediate water. The globally recognized “mid-Maastrichtian event” ∼69 Ma, manifested by the brief appearance of abundant inoceramid bivalves over shallow portions of Shatsky Rise, is characterized by an abrupt increase (∼2°–3°C) in sea surface temperatures, a greater flux of organic matter out of the surface ocean, and warmer (∼4°C) intermediate waters. Results implicate simultaneous changes in surface waters and the sources/distribution patterns of intermediate water masses as an underlying cause for widespread biotic and oceanographic changes during mid-Maastrichtian time.