Prior knowledge activation is foundational to students’ text comprehension. Yet, pedagogical techniques that teachers can use to prompt students’ knowledge activation are limited and empirical data on the relative effectiveness of those techniques is scant. Thus, the purpose of this dissertation was to investigate the effectiveness of traditional and novel knowledge activation techniques for supporting rural students’ comprehension of texts covering unfamiliar content. In this quasi-experimental study, 149 rural middle-school students were assigned to one of three conditions: knowledge mobilization (traditional), relational reasoning (new), or text annotation (control). Data were analyzed using structural equation modeling with text comprehension as the outcome variable and condition, relational reasoning ability, prior topic knowledge, gender, ethnicity, and grade level as predictor variables. The results demonstrated a statistically significant difference for overall comprehension between students in the relational reasoning condition and students in both the mobilization (β = 5.15, p < .00) and control conditions (β = 3.10, p < .00). There were no significant differences between students in the mobilization versus control conditions (β = -1.85, p = .07). Further, there were no comprehension differences for ethnic background or grade level. However, female students outperformed male students, and prior topic knowledge and relational reasoning ability were significant covariates in analysis. Qualitative analysis of follow-up conversations revealed the utility of the relational reasoning condition, especially for low-performing students. The results indicate that not all prior knowledge activation techniques are equally effective for all students engaged in the processing unfamiliar textual content. Additionally, the novel activation technique of relational reasoning proved highly effective for promoting students’ text comprehension.