AbstractThis study presents an overview of the Late Cenozoic evolution of the West African Monsoon (WAM), and the associated changes in atmospheric dynamics and oxygen isotopic composition of precipitation (δ18Op). This evolution is established by using the high‐resolution isotope‐enabled GCM ECHAM5‐wiso to simulate the climatic responses to paleoenvironmental changes during the Mid‐Holocene (MH), Last Glacial Maximum (LGM), and Mid‐Pliocene (MP). The simulated responses are compared to a set of GCM outputs from Paleoclimate Model Intercomparison Project Phase 4 (PMIP4) to assess the added value of a high resolution and model consistency across different time periods. Results show WAM magnitudes and pattern changes that are consistent with PMIP4 models and proxy reconstructions. ECHAM5‐wiso estimates the highest WAM intensification in the MH, with a precipitation increase of up to 150 mm/month reaching 25°N during the monsoon season. The WAM intensification in the MP estimated by ECHAM5‐wiso (up to 80 mm/month) aligns with the mid‐range of the PMIP4 estimates, while the LGM dryness magnitude matches most of the models. Despite an enhanced hydrological cycle in MP, MH simulations indicate a ∼50% precipitation increase and a greater northward extent of WAM than the MP simulations. Strengthened conditions of the WAM in the MH and MP result from a pronounced meridional temperature gradient driving low‐level westerly, Sahel‐Sahara vegetation expansion, and a northward shift of the Africa Easterly Jet. The simulated δ18Op values patterns and their relationship with temperature and precipitation are non‐stationarity over time, emphasizing the implications of assuming stationarity in proxy reconstruction transfer functions.