In Japan, many high school students have severe depression. Preventive interventions for school-based cognitive-behavioral depression are effective countermeasures against depressive problems among high school students. However, since high school curriculums are time-consuming, such interventions are less common among high school students. Therefore, we conducted a long-term but low-frequency intervention that divides the program content through several grades. We examined the effectiveness of our intervention based on the data obtained by a survey during the two-year intervention period and one-year follow-up period for 225 students who had enrolled in 2014-2019. Three-level hierarchical linear model analysis showed that students who participated in the program had improved depressive symptoms and related factors over these three years. The Welch test and chi-square test showed fewer depressive symptoms and a lower percentage of students with depression than the 608 Japanese students who did not receive the intervention; data were collected through an online survey at the end of the program and one year after the intervention ended. The results suggest that a school-based cognitive-behavioral depression prevention program using a long-term but low-frequency approach may effectively reduce the implementation burden into the school curriculum, promote sustained implementation, and prevent depression among high school students.