Apolipoprotein A-I (ApoA-I) - a 243-residue amphipathic protein containing an N-terminal globular domain and a primarily helical C-terminal lipid binding domain - is a principal protein component of high-density lipoprotein (HDL) or \"good\" cholesterol, which is an important component of lipid homeostasis in humans. Synthesized in the liver and intestine and excreted in the blood, ApoA-I undergoes complex, cooperative, and dynamic self-assembly with membrane lipids producing unlipidated (or weakly lapidated), nascent discoidal, and mature HDL states. In vitro studies establish that the recombination of purified protein and lipids reconstitutes this cooperative self-assembly. However, the kinetic pathways by which these mesoscopic, proteolipidic assemblies form remain incompletely understood. Here, we monitor the dynamics of ApoA-I-membrane interactions through real-time monitoring of morphological changes, which ensue when ApoA-I is incubated with minimal giant unilamellar vesicles (GUVs) composed of single phospholipids or phase-separating phospholipid-cholesterol mixtures. Our fluorescence and atomic force microscopy measurements reveal that the interaction produces discoidal particles while remodeling the parent vesicle in discrete stages involving membrane poration, solute leakage, vesiculation, and lipid-lipid phase separation. We find that the qualitative phenomenology is robust and fully reproducible for different protein mutants and alleles (WT APOA-1, {Delta}49ApoA-I, ApoE-3, and ApoE-4) and different lipid mixtures (PC, PC+PS), we tested. Our molecular simulations recapitulate the essential shape changes and further reveal the composition dependence of the interactions. Together, these findings depict key steps in the protein-lipid interactions, which guide the assembly of mesoscopic reconstituted lipoproteins and nanodiscs.