The objective of this study was to analyze morphologically the all-etching bonding system and self-etching bonding system for enamel with different degrees of fluorosis and evaluate the bond strength of each system. Teeth that were indicated for extraction owing to orthodontic or periodontal problems were selected. According to Dean’s index and the Thylstrup-Fejerskov index, 180 extracted teeth were divided into three groups of mild, moderate, and severe dental fluorosis (DF), with 60 teeth in each group. The teeth in each group were randomly divided into two subgroups (n = 30), which were then subjected to the all-etching bonding system (Prime & Bond NT) and self-etching bonding system (SE-Bond). Each group of adhesives was used to bond Z350 universal resin (3M) to the etched dental enamel. Tensile and shear tests were conducted to determine the bond strength. Subsequently, the fractured specimens were investigated using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The Prime & Bond NT was statistically significant for the tensile and shear strength of enamel with mild fluorosis (P < 0.05) but did not exhibit a significant difference for moderate and severe DF (P > 0.05). The SE-Bond was not statistically significant for the tensile and shear strength of mild, moderate, or severe DF (P > 0.05). The SEM and CLSM results reveal that the mild fluorosis enamel crystals were relatively dense, and a small amount of resin remained. The moderate fluorosis enamel crystals were loosely arranged, and the gaps were widened. The severe fluorosis enamel crystals were irregularly arranged. The disorder was aggravated, and the dentinal orifice was exposed by partial enamel exfoliation. The bonding strength of mild fluorosis enamel with the Prime & Bond NT was better than that with the SE-Bond, and cohesive failure was the most common mode of failure. Because there was no difference in the bonding strength of the SE-Bond for different degrees of DF, we recommend the use of the all-etching adhesive system in the clinical treatment of teeth with mild fluorosis.