The joint arrangement in rock masses is the critical factor controlling the stability of rock structures in underground geotechnical engineering. In this study, the influence of the joint inclination angle on the mechanical behavior of jointed rock masses under uniaxial compression was investigated. Physical model laboratory experiments were conducted on jointed specimens with a single pre-existing flaw inclined at 0°, 30°, 45°, 60°, and 90° and on intact specimens. The acoustic emission (AE) signals were monitored during the loading process, which revealed that there is a correlation between the AE characteristics and the failure modes of the jointed specimens with different inclination angles. In addition, particle flow code (PFC) modeling was carried out to reproduce the phenomena observed in the physical experiments. According to the numerical results, the AE phenomenon was basically the same as that observed in the physical experiments. The response of the pre-existing joint mainly involved three stages: (I) the closing of the joint; (II) the strength mobilization of the joint; and (III) the reopening of the joint. Moreover, the response of the pre-existing joint was closely related to the joint’s inclination. As the joint inclination angle increased, the strength mobilization stage of the joint gradually shifted from the pre-peak stage of the stress−strain curve to the post-peak stage. In addition, the instantaneous drop in the average joint system aperture (aave) in the specimens with medium and high inclination angles corresponded to a rapid increase in the form of the pulse of the AE activity during the strength mobilization stage.