Long-term measurements at the Mauna Loa Observatory (MLO) show that the CO2 seasonal cycle amplitude (SCA) increased from 1959 to 2019 at an overall rate of 0.22 ± 0.034 ppm decade-1 while also varying on interannual to decadal time scales. These SCA changes are a signature of changes in land ecological CO2 fluxes as well as shifting winds. Simulations with the TM3 tracer transport model and CO2 fluxes from the Jena CarboScope CO2 Inversion suggest that shifting winds alone have contributed to a decrease in SCA of -0.10 ± 0.022 ppm decade-1 from 1959 to 2019, partly offsetting the observed long-term SCA increase associated with enhanced ecosystem net primary production. According to these simulations and MIROC-ACTM simulations, the shorter-term variability of MLO SCA is nearly equally driven by varying ecological CO2 fluxes (49%) and varying winds (51%). We also show that the MLO SCA is strongly correlated with the Pacific Decadal Oscillation (PDO) due to varying winds, as well as with a closely related wind index (U-PDO). Since 1980, 44% of the wind-driven SCA decrease has been tied to a secular trend in the U-PDO, which is associated with a progressive weakening of westerly winds at 700 mbar over the central Pacific from 20°N to 40°N. Similar impacts of varying winds on the SCA are seen in simulations at other low-latitude Pacific stations, illustrating the difficulty of constraining trend and variability of land CO2 fluxes using observations from low latitudes due to the complexity of circulation changes.