This study evaluated the effectiveness of a newly developed mindfulness and compassion-based social-emotional intervention, Call to Care-Israel (C2C-I), in reducing prejudiced attitudes of Israeli-Jewish youth toward the Israeli-Palestinian outgroup. The C2C-I combines social-cognitive and social-emotional driven mindfulness and compassion practice into one program to create a community of care and cultivate compassion toward the self and others. Three hundred twenty-four Israeli-Jewish 3rd–5th graders (ngirls = 137) from three elementary schools in central Israel were assigned by partial randomization to the C2C-I intervention (nC2CI = 175) or a wait-list control group. Outgroup prejudice was assessed by three measures—stereotyping, affective prejudice, and readiness for social contact—at pre- and post-intervention, as well as at a 6-month follow-up. Results showed that, compared to control group participants, those in the C2C-I intervention significantly reduced affective prejudice toward and negative stereotyping about the Israeli-Palestinian outgroup, while simultaneously increasing their readiness to engage in social contact with Israeli-Palestinian youth. Importantly, the significant effects found in the C2C-I group were maintained at the 6-month follow-up—a period that involved a violent escalation in the Israeli-Palestinian conflict—while further deterioration in intergroup attitudes emerged for the control group. High effect sizes for group differences in all prejudice measures emerged, further highlighting the robust impact of the C2C-I program. These results have significant implications for implementing C2C-I mindfulness and compassion-based practices in order to promote positive intergroup relations in areas characterized by ethnic tension and violent conflict.