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<p>Atmospheric carbon dioxide (<span class="inline-formula">CO₂</span>) accounts for the largest radiative forcing among anthropogenic greenhouse gases. There is, therefore, a pressing need to understand the rate at which <span class="inline-formula">CO₂</span> accumulates in the atmosphere, including the interannual variations (IAVs) in this rate. IAV in the <span class="inline-formula">CO₂</span> growth rate is a small signal relative to the long-term trend and the mean annual cycle of atmospheric <span class="inline-formula">CO₂</span>, and IAV is tied to climatic variations that may provide insights into long-term carbon–climate feedbacks. Observations from the Orbiting Carbon Observatory-2 (OCO-2) mission offer a new opportunity to refine our understanding of atmospheric <span class="inline-formula">CO₂</span> IAV since the satellite can measure over remote terrestrial regions and the open ocean, where traditional in situ <span class="inline-formula">CO₂</span> monitoring is difficult, providing better spatial coverage compared to ground-based monitoring techniques. In this study, we analyze the IAV of column-averaged dry-air <span class="inline-formula">CO₂</span> mole fraction (<span class="inline-formula">XCO₂</span>) from OCO-2 between September 2014 and June 2021. The amplitude of the IAV, which is calculated as the standard deviation of the time series, is up to 1.2 ppm over the continents and around 0.4 ppm over the open ocean. Across all latitudes, the OCO-2-detected <span class="inline-formula">XCO₂</span> IAV shows a clear relationship with El Niño–Southern Oscillation (ENSO)-driven variations that originate in the tropics and are transported poleward. Similar, but smoother, zonal patterns of OCO-2 <span class="inline-formula">XCO₂</span> IAV time series compared to ground-based in situ observations and with column observations<span id="page5356"/> from the Total Carbon Column Observing Network (TCCON) and the Greenhouse Gases Observing Satellite (GOSAT) show that OCO-2 observations can be used reliably to estimate IAV. Furthermore, the extensive spatial coverage of the OCO-2 satellite data leads to smoother IAV time series than those from other datasets, suggesting that OCO-2 provides new capabilities for revealing small IAV signals despite sources of noise and error that are inherent to remote-sensing datasets.</p>