| Restrictions to reduce human interaction have helped to avoid greater suffering and death from the COVID-19 pandemic, but have also created socioeconomic hardship. This disruption is unprecedented in the modern era of global observing networks, pervasive sensing and large-scale tracking of human mobility and behaviour, creating a unique test bed for understanding the Earth System. In this Perspective, we hypothesize the immediate and long-term Earth System responses to COVID-19 along two multidisciplinary cascades: energy, emissions, climate and air quality; and poverty, globalization, food and biodiversity. While short-term impacts are dominated by direct effects arising from reduced human activity, longer-lasting impacts are likely to result from cascading effects of the economic recession on global poverty, green investment and human behaviour. These impacts offer the opportunity for novel insight, particularly with the careful deployment of targeted data collection, coordinated model experiments and solution-oriented randomized controlled trials, during and after the pandemic.