We investigated the combined effects of temperature and pressure on liquid–liquid phase separation (LLPS) phenomena of α‐elastin up to the multi‐kbar regime. FT‐IR spectroscopy, CD, UV/Vis absorption, phase‐contrast light and fluorescence microscopy techniques were employed to reveal structural changes and mesoscopic phase states of the system. A novel pressure‐induced reentrant LLPS was observed in the intermediate temperature range. A molecular‐level picture, in particular on the role of hydrophobic interactions, hydration, and void volume in controlling LLPS phenomena is presented. The potential role of the LLPS phenomena in the development of early cellular compartmentalization is discussed, which might have started in the deep sea, where pressures up to the kbar level are encountered.