The thermal behavior of semicrystalline polymers constitutes a long-standing problem in polymer crystallization. Although it is widely agreed that the crystal thickness resulting from isothermal crystallization is a sharply selected value, the melting behavior of semicrystalline polymers is very complex. In this work, a combination of high-temperature AFM and time- and temperature-resolved SAXS/WAXS was employed to examine the microstructural evolution during isothermal melt-crystallization and subsequent melting of poly(trimethylene terephthalate). The SAXS data were analyzed in the frame of the generalized paracrystalline lamellar stack model. The crystal thickness remains almost constant and uniform throughout the isothermal crystallization and melting. The crystals squeezed between the thinnest amorphous layers melt first. The reciprocal size of the amorphous regions undergoing transformation scales linearly with temperature. A simple model is proposed, which accounts for this confinement-driven melting by a negative pressure imposed on the crystals by the neighboring amorphous regions.