The conjugated polymer poly­(3,4-ethylenedioxythiophene) polymerized and stabilized in the presence of polystyrene­sulfonate (best known as PEDOT:PSS) is a working horse of organic electronics and bioelectronics and one of the most important conductive polymers. While its morphology is complex and depends on the details in synthesis and post-treatment, its distinctive and common feature is a two-phase granular structure attributed to PEDOT- and PSS-rich regions. Yet, there is still no well-established consensus concerning the precise nature of PEDOT- and PSS-rich regions as well as their chemical composition and structure. In this study we perform coarse-grained MARTINI molecular dynamics simulations of PEDOT:PSS focusing on understanding its two-phase morphology as well as water intake and ion exchange. We demonstrate that PEDOT:PSS is an essentially three-component system consisting of positively charged PEDOT chains, PSS chains with mostly deprotonated sulfonate groups, and protonated PSS chains. PEDOT-rich regions are predominantly composed of PEDOT and deprotonated PSS chains, whereas PSS-rich regions are composed of protonated PSS chains. Our calculations unravel how PEDOT- and PSS-rich regions are formed from the solution phase during the drying process. We show that when the dry polymer film is immersed in water, its swells by nearly 60%, and we demonstrate that the origin of swelling is related to deprotonation of the sulfonate groups in the PSS-rich regions. It is mostly PSS-rich regions that swell while the PEDOT-rich regions remain rather unchanged. We demonstrate that swelling of the film is rather insignificant during reduction/oxidation within the cyclic voltammetry (CV) conditions. We show that during CV experiments each counterion brings on overage ≈4 water molecules into the polymer region. Our simulations of swelling, CV experiments, and π–π stacking formation in PEDOT and PSS match well the experimental results. Our theoretical studies unravel the most important morphological aspects of one of the most important polymers for organic electronics, providing the essential insight needed for the material and device design and improvements.