Hybrid organic–inorganic perovskites (HOIPs) with chiral organic ligands exhibit highly spin-dependent transport and strong natural optical activity (NOA). Here we show that these remarkable features can be traced to a chirality-induced spin–orbit coupling (SOC), H so = ατk z σ z , which connects the carrier’s spin (σ z ), its wave vector (k z ), and the material’s helicity (τ) along the screw direction with strength α controlled by the geometry of the organic ligands. This SOC leads to a macroscopic spin polarization in the presence of an electrical current and is responsible for the observed spin-selective transport. NOA originates from a coupling between the exciton’s center-of-mass wave vector K z and its circular polarization j z ex, H so ′ = α′τK z j z ex, contributed jointly from the electron’s and the hole’s SOCs in an exciton. Our model provides a roadmap to achieve a strong and tunable chirality in HOIPs for novel applications utilizing carrier spin and photon polarization.