The purpose of this study was to investigate the impacts of visual cues and different types of self-explanation prompts on learning, cognitive load, and intrinsic motivation in an interactive multimedia environment that was designed to deliver a computer-based lesson about the human cardiovascular system. A total of 126 college students were randomly assigned in equal numbers (N = 21) to one of the six conditions in a 2 × 3 factorial design with visual cueing (cueing vs. no cueing) and type of self-explanation prompts (prediction prompts vs. reflection prompts vs. no prompts) as the between-subjects factors. The results revealed that (a) participants presented with cued animations had significantly higher learning outcome scores than their peers who viewed uncued animations, and (b) cognitive load and intrinsic motivation had different impacts on learning outcomes due to the moderation effect of cueing. The results suggest that the cues may not only enhance learning, but also indirectly impact learning, cognitive load, and intrinsic motivation.