One practical approach towards robust and stable biomimetic platforms is to generate hybrid bilayers that incorporate both lipids and block co-polymer amphiphiles. The currently limited number of reports on the interaction of glass surfaces with hybrid lipid and polymer vesicles—DOPC mixed with amphiphilic poly(ethylene oxide-b-butadiene) (PEO-PBd)—describe substantially different conclusions under very similar conditions (i.e., same pH). In this study, we varied vesicle composition and solution pH in order to generate a broader picture of spontaneous hybrid lipid/polymer vesicle interactions with rigid supports. Using quartz crystal microbalance with dissipation (QCM-D), we followed the interaction of hybrid lipid-polymer vesicles with borosilicate glass as a function of pH. We found pH-dependent adsorption/fusion of hybrid vesicles that accounts for some of the contradictory results observed in previous studies. Our results show that the formation of hybrid lipid-polymer bilayers is highly pH dependent and indicate that the interaction between glass surfaces and hybrid DOPC/PEO-PBd can be tuned with pH.