The natural band alignments of ScxAl1−xN/GaN heterojunctions, with Sc-contents ranging from 0% to 25%, are investigated by first-principles density functional theory with the local density approximation. Type-I ScxAl1−xN/GaN heterojunctions with large conduction band offsets (CBOs) and valence band offsets (VBOs) are found. The band alignment of nearly lattice-matched ScAlN (x = ∼18.75%) with respect to GaN (CBO = 1.74 eV, VBO = 0.34 eV) is also calculated for future implementation in GaN-based quantum wells and power devices. Our findings provide useful band parameters necessary for enabling the implementation of ScAlN alloys in GaN-based power and optoelectronic devices.