We analyze single transverse-spin asymmetries for hadronic pion production at large transverse momenta using QCD factorization. In the large x F region, leading contributions to the asymmetries are naturally produced by twist-3 parton correlation functions that couple quark fields and gluon field strengths. With a simple model for these matrix elements, leading-order asymmetries calculated from QCD are consistent with data on pion production from Fermilab, and can be used to predict single-spin asymmetries at BNL RHIC. We argue that our perturbative calculation for the asymmetries is relevant to pion transverse momenta as low as a few GeV. ͓S0556-2821͑98͒07423-2͔