Abstract Changes in the western North Pacific anomalous anticyclone (WNPAC) are an important bridge that connects the El Niño-Southern Oscillation (ENSO) and East Asian climate variability. Investigation of the WNPAC across the Last Interglacial (LIG, 130–120 ka), the warmest interglacial during the past 800 ka driven by Earth’s orbit, may advance our knowledge on East Asian climate change in a warmer-than-present world. Based on the Transient Global Climate Simulation covering the LIG (TGCS-LIG), we found a long-term strengthened trend of the WNPAC in an El Niño-decaying summer from the early LIG (130–129 ka, 0.5 gpm ℃ −1 ) to the late LIG (121–120 ka, 2.7 gpm ℃ −1 ). The strengthened WNPAC during the late LIG relative to the early was manifested by El Niño-induced anomalous easterly wind over the tropical western Pacific and enhanced geopotential height over the western North Pacific at 850 hPa. The strengthened WNPAC was jointly driven by anomalous cooling of the tropical Pacific Ocean and the warming of the tropical Indian Ocean, with the contribution from the cooling of the western North Pacific in an El Niño-decaying summer during the late LIG relative to the early. We speculated that the decreased annual cycle of solar insolation over the subtropics may drive the long-term strengthened trend of the WNPAC across the LIG, with the contribution from greenhouse gases. Our results highlighted the strengthened WNPAC across the LIG in response to the precession, which may provide insights for predicting East Asian interannual climate variability in a warmer-than-present world.