Antimony sesquisulfide Sb2S3 has become an outstanding advanced functional material in a variety of rapidly growing application fields: smart integrated photonics from the visible to telecom window, cost-efficient photovoltaics, energy storage and transformation. Rational design and tailoring of the required components need a deep insight into the atomic structure and dynamics of liquid and amorphous Sb2S3, but detailed information is missing in contrast to crystalline counterparts. Using high-energy X-ray diffraction and Raman spectroscopy over an extended temperature range, supported by first-principles simulations as well as by electrical and thermal studies, we show that the high optical and electric contrast between the SET (crystalline) and RESET (amorphous) logic states is related to the different short and intermediate range order in orthorhombic and vitreous Sb2S3. It includes strong asymmetry of the Sb–S nearest neighbor distances and a different coordination of antimony sites in the crystal vs. a distorted trigonal environment of defect octahedral SbS3 entities in glassy Sb2S3. A fast crystallization rate at elevated temperatures in liquid antimony sesquisulfide is related to the enhanced fragility, approaching that of telluride phase-change materials, and to a large fraction of ABAB squares (A: Sb; B: S), combined with a remarkable slowdown of the diffusion processes in the vicinity of the glass transition temperature, ensuring good retention of the amorphous state. Further improvements may be achieved using anionic (Se) or cationic (Bi) substitution that decreases the temperature of a semiconductor–metal transition and allows bandgap engineering, important for both photonics and photovoltaics.