This study aims to investigate the gradient nanomechanical behavior of dental fluorosis enamel and provide appropriate selection criteria for restorative materials. The nanomechanical properties of the outer, middle, and inner layers of normal tooth enamel, mild dental fluorosis enamel, and severe dental fluorosis enamel were tested by nanoindentation under an applied load of 2000 μN and holding time of 30 s. The nanotribological properties were then evaluated through nanoscratch tests under an applied load of 1000 μN. In addition, the nanotribological property of the outer layer of dental fluorosis enamel was compared with that of four restorative materials, namely, lithium disilicate glass-ceramic (IPS e.max CAD), polymer-infiltrated-ceramic network (PICN), composite resin block (Lava™ ultimate), and conventional composite resin (Fltek™ Z350XT). The nanohardness and elastic modulus of mild dental fluorosis enamel increased from the outer to the middle layers and then decreased from the middle to the inner layers. By contrast, the changed displacement, friction coefficient, and nanoscratch depth and width decreased from the outer to the middle layers and then increased from the middle to the inner layers. In severe dental fluorosis enamel, nanohardness and elastic modulus increased from the outer to the inner layers, but the changed displacement, friction coefficient, and nanoscratch depth and width decreased from the outer to the inner layers. The nanoscratch depth and width of Lava™ ultimate were similar to those of the outer layer of the mild dental fluorosis enamel. The gradient nanomechanical behavior of dental fluorosis enamel significantly differed from that of normal tooth enamel. Dental materials with a wear resistance similar to that of the opposing enamel are a good choice for restoring dental fluorosis (trial registration: WCHSIRB-D-2014-126, registered 25 December 2014).