The interdecadal variability of cross-equatorial meridional winds in the eastern Pacific (V_EP), which has been shown to correlate to the amplitude of El Niño-Southern Oscillation (ENSO) on the interdecadal timescale, is investigated using long-term observations and 22 models from the Coupled Model Intercomparison Project Phase 6 (CMIP6). Both observations and models exhibit a tight negative correlation between interannual variations of V_EP and ENSO and this relationship is synchronized with the interdecadal variability of V_EP. In long-term observations, ENSO amplitude modulation is still seen to be out-of-phase with interdecadal variability of V_EP. This relationship, however, is substantially underestimated among CMIP6 models, particularly in the historical simulations. The interdecadal variability of V_EP is associated with both the Interdecadal Pacific Oscillation (IPO) and the Atlantic Multidecadal Oscillation (AMO) in observations. However, most CMIP6 pre-industrial control (PI-control) experiments have no link between the V_EP and AMO. In contrast, in historical simulations, the multimodel mean of interdecadal V_EP shows a significant fluctuation with AMO around the 1980s, which might be caused by the anthropogenic aerosol forcing. Consequently, the interdecadal variation of the AMO-V_EP relationship is likely a response to external forcing while the IPO-V_EP relationship is mainly modulated by internal climate variability. Another plausible factor causing the weak AMO-V_EP relationship in PI-control runs is the unrealistic relationship between modelled SSTs in the tropical Pacific and North Atlantic. Furthermore, model biases in the tropical Pacific may account for the weak relationship between interdecadal V_EP and ENSO amplitude in CMIP6 models.