Organic two-dimensional crystals (O2DCs) are a class of synthetic layered materials, typically constructed from π-conjugated building blocks, that show extended in-plane π-conjugation and/or interlayer electronic couplings. They are synthesized either directly as monolayer to few-layer nanosheets or as bulk crystals that can be exfoliated. O2DCs display customizable topological structures and layer-dependent physical attributes, offering a versatile material platform for exploring intriguing electronic and quantum phenomena. In this Review, we discuss the structure–property relationships and synthetic strategies of O2DCs, with particular emphasis on their unique electronic structures, charge transport properties and the emergence of quantum states, such as topological and superconducting phases, alongside different spin states. Furthermore, we highlight emerging device applications of O2DCs across electronics, optoelectronics and spintronics. Finally, we provide an outlook on the persistent challenges in synthetic chemistry, physics and materials science that must be addressed to further advance this field.