Four-dimensional (4D) electron microscopy (EM) uniquely combines the high spatial resolution to pinpoint individual nano-objects, with the high temporal resolution necessary to address the dynamics of their laser-induced transformation. Here, using 4D-EM, we demonstrate the in situ irreversible transformation of individual nanoparticles of the molecular framework Fe(pyrazine)Pt(CN)4. The newly formed material exhibits an unusually large negative thermal expansion (i.e. contraction), which is revealed by time-resolved imaging and diffraction. Negative thermal expansion is a unique property exhibited by only few materials. Here we show that the increased flexibility of the metal–cyanide framework after the removal of the bridging pyrazine ligands is responsible for the negative thermal expansion behavior of the new material. This in situ visualization of single nanostructures during reactions should be extendable to other classes of reactive systems.