With synthetic ease and tunable degradation lifetimes, poly(β-amino ester)s (PBAEs) have found use in increasingly diverse applications, from gene therapy to thermosets. Protonatable amines in each repeating unit impart pH-dependent solution behavior and lifetimes, with acidic conditions favoring solubility, yet slowing hydrolysis. Due in part to these interconnected phenomena governing pH-dependent PBAE degradation, predictive degradation models, which would enable user-defined lifetimes, remain elusive. To separate the effects of charge state and solution pH on PBAE degradation, we synthesized poly(β-quaternary ammonium ester)s (PBQAEs), which differ from their parent PBAEs only by an additional methyl group, generating polymers with pH-independent cationic charge. Like PBAEs, PBQAE hydrolysis accelerates with increasing pH, although at a given pH, PBAE degradation outpaces PBQAE degradation. This difference is more pronounced in basic solutions, suggesting that deprotonated PBAE amines accelerate hydrolysis, providing an additional tuning parameter to PBAE lifetime and informing the degradation of PBAEs and other pH-responsive polymers.