Adolescence is a critical developmental stage that is particularly vulnerable to the initiation of tobacco use. Despite the well-documented health risks associated with tobacco use, it remains prevalent among adolescents. Games for health are a promising strategy for tobacco prevention, using experiential and social learning theories to enhance engagement and improve behavior change. This pilot study aims to (1) compare the social game-based program Storm-Heroes to a nonsocial program regarding adolescents' personal and social experiences and (2) examine how these experiences predict higher tobacco knowledge and perceived risks of vaping and conventional tobacco use. In a cluster-randomized comparative design, 4 after-school sites (N=79 adolescents) were recruited in person and randomized in a single-blinded format to 1 of 2 interventions: the social game Storm-Heroes (44/79, 56%) or the nonsocial program A Smoking Prevention Interactive Experience (ASPIRE; 35/79, 44%). A study team member supervised both interventions. Data were collected at baseline, immediate follow-up, and a 1.5-month follow-up (45/74, 61% retained). Repeated measures mixed effects models were conducted. A total of 45 participants continued until the 1.5-month follow-up. Participants in the Strom-Heroes group were more likely to increase their perceived risk of vaping (B=0.40; P<.001), perceived risk of conventional tobacco use (B=0.35; P=.046), and tobacco knowledge (B=1.63; P<.001) than those in the control condition. The usability level of the program was related to a higher perceived risk of vaping (B=0.16; P=.003) and conventional tobacco use (B=0.16; P=.02) by follow-up. Attention to the program was also related to higher perceived risk of vaping (B=0.12; P=.002) and conventional tobacco use (B=0.14; P<.001). Distraction was not related to either perceived risk of vaping (P=.15) or perceived risk of conventional tobacco use (P=.71). In contrast, both more attention (B=0.60; P<.001) and less distraction (B=-0.37; P<.001) were related to higher tobacco knowledge. The increased perceived risk of vaping and conventional tobacco among Storm-Heroes participants aligns with the program's goals of improving participants' awareness of the risks associated with tobacco use and their tobacco knowledge. However, distraction weakened the effect of the program on tobacco knowledge, indicating that emphasis needs to be placed on minimizing distraction for better outcomes. With the results of this study, researchers can work to advance the current version of Storm-Heroes and amplify engagement in the program to improve its potential for preventing adolescents' initiation of tobacco use. ClinicalTrials.gov NCT02703597; https://clinicaltrials.gov/study/NCT02703597.