AbstractAcross the middle Miocene, Earth's climate underwent a major cooling and expansion of the Antarctic ice sheet. However, the associated response and development of the tropical climate system is not fully understood, in part because this is influenced by both global climate and also low‐latitude tectonic gateways and paleoceanography. Here we use combined δ18O and Mg/Ca of planktic foraminifera to reconstruct the thermal history and changes in hydrology from the Indo‐Pacific region from 16.5 to 11.5 Ma. During the warmth of the early middle Miocene, our records indicate a dynamic ocean‐atmosphere system in the Indo‐Pacific region, with episodes of saltier and warmer tropical surface waters associated with high pCO2 and retreat of the Antarctic ice sheet. We show that across the Middle Miocene Climate Transition (MMCT) surface ocean temperatures in the Indo‐Pacific cooled by ~2°C, synchronous with the advance of the Antarctic ice sheet. The associated cooling in the Southern Ocean appears to have started earlier and was stronger. Further, we show that western Pacific Ocean warmed and eastern tropical Indian Ocean freshened following the MMCT, likely caused by the constriction of the Indonesian Seaway and reduced connectivity between the Pacific and Indian Oceans following Antarctic glaciation. The MMCT therefore represented a key phase in the evolution of the West Pacific Warm Pool and associated tropical climate dynamics.