Polymer-supported bilayers (PSBs) are a recognized tool for drug discovery through function-interaction analysis of membrane proteins. While silica-supported bilayers (SSBs) spontaneously form from surface-adsorbed vesicles, successful PSB formation via a similar method has thus far been limited by an insufficient understanding of the underlying vesicle-remodelling processes. Here, we generated a polymer support through the incubation of poly-L-lysine conjugated to alkyl-chain-terminated poly(ethylene)glycol on silica. This polymer-coated silica substrate yielded efficient vesicle adsorption and spontaneous bilayer formation, thereby providing a rare opportunity to address the mechanism of PSB formation and compare it to that of SSB. The combined use of super-resolution imaging, kinetics, and simulations indicates that the rupture of stochastically formed vesicle clusters is the rate-limiting step, which is an order of magnitude higher for silica than for polymer-coated silica. This was confirmed by directly demonstrating increased rupture rates for surface adsorbed multivesicle assemblies formed by vesicle cross-linking in solution. On the basis of this key insight we surmised that a low propensity of cluster rupture can be compensated for by an increase in the number density of clusters: the deposition of a mixture of oppositely charged vesicles resulted in bilayer formation on another alkane PEG type of interface, which despite efficient vesicle adsorption otherwise fails to support spontaneous bilayer formation. This potentially provides a universal strategy for promoting bilayer formation on resistant surfaces without resorting to modifying the surface itself. Therefore, multivesicle assemblies with tailored geometries not only could facilitate bilayer formation on polymers with interesting functional properties but also could instigate the exploration of vesicle architecture for other processes involving vesicle remodelling such as drug delivery.