Collision and disruption processes of protoplanetary bodies in the early Solar System are key to understanding the genesis of diverse types of main-belt asteroids. Mesosiderites are stony-iron meteorites that formed by the mixing of howardite–eucrite–diogenite-like crust and molten core materials and provide unique insights into the catastrophic break-up of differentiated asteroids. However, the enigmatic formation process and the poorly constrained timing of metal–silicate mixing complicate the assignment to potential parent bodies. Here we report the high-precision uranium–lead dating of mesosiderite zircons by isotope dilution thermal ionization mass spectrometry to reveal an initial crust formation 4,558.5 ± 2.1 million years ago and metal–silicate mixing at 4,525.39 ± 0.85 million years ago. The two distinct ages coincide with the timing of the crust formation and a large-scale reheating event on the eucrite parent body, probably the asteroid Vesta. This chronological coincidence corroborates that Vesta is the parent body of mesosiderite silicates. Mesosiderite formation on Vesta can be explained by a hit-and-run collision 4,525.4 million years ago that caused the thick crust observed by NASA’s Dawn mission and explains the missing olivine in mesosiderites, howardite–eucrite–diogenite meteorites and vestoids.