The exchange is critical for designing high-performance Nd-Fe-B permanent magnets. Here we demonstrate through multiscale simulations that the exchange in Nd-Fe-B magnets, including bulk exchange stiffness (A e) in Nd 2 Fe 14 B phase and interface exchange coupling strength (J int) between Nd 2 Fe 14 B and grain boundary (GB), is strongly anisotropic. A e is larger along crystallographic a/b axis than along c axis. Even when the GB Fe x Nd 1−x has the same composition, J int for (100) interface is much higher than that for (001) interface. The discovered anisotropic exchange is shown to have profound influence on the coercivity. These findings enable more freedom in designing Nd-Fe-B magnets by tuning exchange. IMPACT STATEMENT Bulk exchange stiffness in Nd 2 Fe 14 B and interface exchange coupling strength between Nd 2 Fe 14 B and grain boundary are found strongly anisotropic, which have profound influence on the coercivity of Nd-Fe-B magnets.