Axions and axion-like particles (ALPs) are well-motivated low-energy relics of high-energy extensions of the Standard Model (SM). We investigate the phenomenology of an ALP with flavor-changing couplings, and present a comprehensive analysis of quark and lepton flavor-changing observables within a general ALP effective field theory. Observables studied include rare meson decays, flavor oscillations of neutral mesons, rare lepton decays, and dipole moments. We derive bounds on the general ALP couplings as a function of its mass, consistently taking into account the ALP lifetime and branching ratios. We further calculate quark flavor-changing effects that are unavoidably induced by running and matching between the new physics scale and the scale of the measurements. This allows us to derive bounds on benchmark ALP models in which only a single (flavorless or flavor-universal) ALP coupling to SM particles is present at the new physics scale, and in this context we highlight the complementarity and competitiveness of flavor bounds with constraints derived from collider, beam dump and astrophysical measurements. We find that searches for ALPs produced in meson decays provide some of the strongest constraints in the MeV-GeV mass range, even for the most flavorless of ALP models. Likewise, we discuss the interplay of flavor-conserving and flavor-violating couplings of the ALP to leptons, finding that constraints from lepton flavor-violating observables generally depend strongly on both. Additionally, we analyze whether an ALP can provide an explanation for various experimental anomalies including those observed in rare B-meson decays, measurements at the ATOMKI and KTeV experiments, and in the anomalous magnetic moments of the muon and the electron.