Recent variability in West African monsoon rainfall (WAMR) has been shown to be influenced by multiple ocean–atmosphere modes, including the El Niño Southern Oscillation, Atlantic Multidecadal Oscillation and the Interdecadal Pacific Oscillation. How these modes will change in response to long term forcing is less well understood. Here we use four transient simulations driven by changes in orbital forcing and greenhouse gas concentrations over the past 6000 years to examine the relationship between West African monsoon rainfall multiscale variability and changes in the modes associated with this variability. All four models show a near linear decline in monsoon rainfall over the past 6000 years in response to the gradual weakening of the interhemispheric gradient in sea surface temperatures. The only indices that show a long-term trend are those associated with the strengthening of the El Niño Southern Oscillation from the mid-Holocene onwards. At the interannual-to-decadal timescale, WAMR variability is largely influenced by Pacific–Atlantic – Mediterranean Sea teleconnections in all simulations; the exact configurations are model sensitive. The WAMR interannual-to-decadal variability depicts marked multi-centennial oscillations, with La Niña/negative Pacific Decadal Oscillation and a weakening and/or poleward shift of subtropical high-pressure systems over the Atlantic favoring wet WAMR anomalies. The WAMR interannual-to-decadal variability also depicts an overall decreasing trend throughout the Holocene that is consistent among the simulations. This decreasing trend relates to changes in the North Atlantic and Gulf of Guinea Sea Surface Temperature variability.