In December 2018, an unusually large intra- and extra-caldera eruption took place at Ambrym volcano (Vanuatu). The eruption drained the volcano’s five active lava lakes and terminated, at least momentarily, the surface activity that had been ongoing for decades to hundreds of years, sustaining the largest recorded persistent degassing on the planet. Here, we investigate the mechanisms and dynamics of this major eruption. We use major elements and volatiles in olivine and clinopyroxene-hosted melt inclusions, embayments, crystals and matrix glasses together with clinopyroxene geobarometry as well as olivine and clinopyroxene geothermometry and diffusion modelling in crystals and embayments to reconstruct the chronology and timing of the subsurface processes that accompanied the eruption. We find that the eruption began with the meeting, mingling and limited chemical mixing of mostly two magma bodies occupying similar vertical but different horizontal locations in the crust, one corresponding to the main plumbing system at Ambrym that fed the lava lakes and the other corresponding to an older, previously cutoff and more chemically evolved branch of the plumbing system. Within the primitive magma, two texturally distinct components—one microlite rich and one microlite poor—can further be identified. The 2018 eruption hence provides a detailed image of Ambrym’s complex plumbing system. Our diffusion timescales and geobarometric estimates coincide closely with geophysical observations. They point to a reconnection of the evolved magmatic branch with the main system occurring less than 10 h prior to the intra-caldera eruption and a period of 2 days for the subsequent > 30-km lateral magma transport along a deeper dike prior to submarine eruption just off the SE coast of the island with the more primitive magma reaching first followed by mingled magma containing both compositions. Magma ascent rates are estimated at 95 ± 24 m/s in the last ~ 2.5 km of ascent during the intra-caldera eruption and at 80 ± 6 m/s in the last ~ 4 km of ascent during the submarine eruption. Comparison with other lava lake draining eruptions reveals striking similarities both in terms of precursory activity, with lake level rising prior to the eruption in all cases, and in terms of plumbing system organization with the presence of peripheral magma pockets, isolated from the main magmatic system but that can be mobilized and erupted when met by dikes propagating laterally from the main system.