To better understand instructional cognitive load, it is important to operationalize and assess it in novel ways that can reveal how different students perceive and experience this load as either challenging or threatening. The present study administered a recently developed instruction assessment tool—the Load Reduction Instruction Scale-Short (LRIS-S)—to N = 2,071 students in 188 high school science classrooms. Multilevel latent profile analysis (LPA) was used to identify student and classroom profiles based on students' reports of instructional cognitive load (load reduction instruction, LRI; using the LRIS-S) and their accompanying psychological challenge orientations (self-efficacy and growth goals), and psychological threat orientations (anxiety and failure avoidance goals). In phase 1 of analyses (investigating students; Level 1), we identified 5 instructional-psychological student profiles that represented different presentations of instructional load, challenge orientation, and threat orientation, ranging from the most maladaptive profile (the Instructionally-Overburdened & Psychologically-Resigned profile) to the most adaptive profile (Instructionally-Optimized & Psychologically-Self-Assured profile). The derived profiles revealed that similar levels of perceived instructional load can be accompanied by different levels of perceived challenge and threat. For example, we identified two profiles that were both instructionally-supported but who varied in their accompanying psychological orientations. Findings also identified profiles where students were dually motivated by both challenge and threat. In turn, these profiles (and their component scores) were validated through their significant associations with persistence, disengagement, and achievement. In phase 2 of analyses (investigating students and classrooms; Levels 1 and 2), we identified 3 instructional-psychological classroom profiles that varied in instructional cognitive load, challenge orientations, and threat orientations: Striving classrooms, Thriving classrooms, and Struggling classrooms. These three classroom profiles (and their component scores) were also validated through their significant associations with classroom-average persistence, disengagement, and achievement—with Struggling classrooms reflecting the most maladaptive outcomes and Thriving classrooms reflecting the most adaptive outcomes. Taken together, findings show that considering instructional cognitive load (and new approaches to empirically assessing it) in the context of students' accompanying psychological orientations can reveal unique insights about students' learning experiences and about important differences between classrooms in terms of the instructional load that is present.