Merapi volcano (Indonesia) is one of the most active and hazardous volcanoes in the world. It is known for frequent small to moderate eruptions, pyroclastic flows produced by lava dome collapse, and the large population settled on and around the flanks of the volcano that is at risk. Its usual behavior for the last decades abruptly changed in late October and early November 2010, when the volcano produced its largest and most explosive eruptions in more than a century, displacing at least a third of a million people, and claiming nearly 400 lives. Despite the challenges involved in forecasting this ‘hundred year eruption’, we show that the magnitude of precursory signals (seismicity, ground deformation, gas emissions) was proportional to the large size and intensity of the eruption. In addition and for the first time, near-real-time satellite radar imagery played an equal role with seismic, geodetic, and gas observations in monitoring eruptive activity during a major volcanic crisis. The Indonesian Center of Volcanology and Geological Hazard Mitigation (CVGHM) issued timely forecasts of the magnitude of the eruption phases, saving 10,000–20,000 lives. In addition to reporting on aspects of the crisis management, we report the first synthesis of scientific observations of the eruption. Our monitoring and petrologic data show that the 2010 eruption was fed by rapid ascent of magma from depths ranging from 5 to 30 km. Magma reached the surface with variable gas content resulting in alternating explosive and rapid effusive eruptions, and released a total of ~ 0.44 Tg of SO₂. The eruptive behavior seems also related to the seismicity along a tectonic fault more than 40 km from the volcano, highlighting both the complex stress pattern of the Merapi region of Java and the role of magmatic pressurization in activating regional faults. We suggest a dynamic triggering of the main explosions on 3 and 4 November by the passing seismic waves generated by regional earthquakes on these days.