Background Screenshots is an in-school curriculum that seeks to develop positive digital social skills in middle school students with the long-term goal of improving their health and well-being. The program imparts knowledge and teaches skills upon which young adolescents can build a set of beliefs and behaviors that foster respectful interactions, prosocial conflict resolutions, and safe and secure use of communication technology. Intervening in this way can improve young people’s mental health by limiting their exposure to cyberbullying and other forms of negative online interactions. This study reports on an evaluation of the Screenshots program conducted with seventh graders in a public school system in a midsized New England city. Objective This study aims to determine the effectiveness of the Screenshots program in increasing participants’ knowledge about key concepts of digital citizenship and in shifting beliefs and intended behaviors to align with prosocial and safe online interactions. In addition, the study examines whether the program has varying effects on males’ and females’ conflict and bullying resolution strategies. Methods This quasi-experimental evaluation was conducted in four middle schools in which one group of seventh graders received the Screenshots curriculum and another did not. Before and after the curriculum, all students completed a questionnaire that measured their knowledge of and beliefs about digital citizenship and related online behavioral concepts, their attitudes regarding strategies for stopping online bullying, and their intended online conflict resolution behaviors. Results The sample included 92 students who received the curriculum and 71 students who were included in the comparison group. Pre- to postinstruction retention rates ranged from 52% (33/63) to 84% (21/25), varying by school and condition. The results showed an increase in knowledge about key curricular concepts for some students (F1,32=9.97; P=.003). In response to some individual items, students decreased their belief supportive of a negative online behavior (F1,76=9.00; P=.004) and increased their belief consistent with an online safety behavior (F1,42=4.39; P=.04) compared with the comparison group. Gender moderated the results related to conflict resolution, with males from one school reducing their endorsement of an aggressive option (F2,40=5.77; P=.006) and males from another school increasing their reported tendency to pursue a nonaggressive option (F2,28=3.65; P=.04). On average, participants reported learning something new from the classes. Conclusions This study represents a rare evaluation of an in-school digital citizenship program and demonstrates the effectiveness of Screenshots. Students’ increased knowledge of key curricular concepts represents a foundation for developing future beliefs and healthy behaviors. Differences in how adolescent males and females experience and perpetrate online aggression likely explain the conflict resolution findings and emphasize the need to examine gender differences in response to these programs. Students’ high ratings of the relevance of Screenshots’ content reinforce the need for this type of intervention.