We characterize spatial–temporal patterns of interannual variability (IAV) in atmospheric CO₂ based on NASA’s Orbiting Carbon Observatory-2 (OCO-2). CO₂ variation is strongly impacted by climate events, with higher anomalies during El Nino years. We show high correlation in IAV between space-based and ground-based CO₂ from long-term sites. Because OCO-2 has near-global coverage, our paper provides a roadmap to study IAV where in situ observation is sparse, such as open oceans and remote lands.