Maintaining lipid asymmetry across membrane leaflets is critical for functions like vesicular traffic and organelle homeostasis. However, a lack of molecular‐level understanding of the mechanisms underlying membrane fission and fusion processes in synthetic systems precludes their development as artificial analogs. Here, we report asymmetry induction of a bilayer membrane formed by an extended π‐conjugated molecule with oxyalkylene side chains bearing terminal tertiary amine moieties (BA1) in water. Autogenous protonation of the tertiary amines in the periphery of the bilayer by water induces anisotropic curvature, resulting in membrane fission to form vesicles and can be monitored using time‐dependent spectroscopy and microscopy. Interestingly, upon loss of the induced asymmetry by extensive protonation using an organic acid restored bilayer membrane. The mechanism leading to the compositional asymmetry in the leaflet and curvature induction in the membrane is validated by density functional theory (DFT) calculations. Studies extended to control molecules having changes in hydrophilic (BA2) and hydrophobic (BA3) segments provide insight into the delicate nature of molecular scale interactions in the dynamic transformation of supramolecular structures. The synergic effect of hydrophobic interaction and the hydrated state of BA1 aggregates provide dynamicity and unusual stability. Our study unveils mechanistic insight into the dynamic transformation of bilayer membranes into vesicles. Spontaneous curvature induction in an artificial supramolecular bilayer membrane and its transformation into vesicles in pure water is demonstrated. Compositional asymmetry resulting from the autogenous protonation of amines led to the formation of an asymmetric membrane and curvature induction. The stability provided by the hydrophobic interaction and the hydrated state of the supramolecular structure in water appears to be critical in the dynamic morphological transformations.