Transformation of flat membrane into round vesicles is generally thought to underlie endocytosis and produce speed-, amount- and vesicle-size-specific endocytic modes. Visualizing depolarization-induced exocytosis and subsequent endocytic transformation in live neuroendocrine chromaffin cells, we found that flat membrane is transformed into Λ-shape, Ω-shape and then O-shape vesicles via membrane invagination, Λ-base constriction and Ω-pore constriction, respectively. Surprisingly, endocytic vesicle formation is predominantly not from flat-membrane-to-round-vesicle transformation, but from calcium-triggered and dynamin-mediated closure of 1) Ω-profiles formed before depolarization and 2) fusion pores (called kiss-and-run). Varying calcium influxes control these pore closures’ speed, number, and vesicle size, resulting in speed-specific slow (>~6-s), fast (<~6-s) or ultrafast (<0.6-s) endocytosis, amount-specific compensatory (endocytosis=exocytosis) or overshoot endocytosis (endocytosis>exocytosis), and size-specific bulk endocytosis. These findings reveal major membrane transformation mechanisms underlying endocytosis, diverse endocytic modes, and exo-endocytosis coupling in neuroendocrine cells, challenging the half-a-century concept that the flat-to-round transformation predominantly mediates endocytosis after physiological stimulation.