The goal of this dissertation is twofold: to assess anti-smoking campaign effects, and examine the ad-induced, cognitive processes that account for effective anti-smoking advertisements. The dissertation studies evaluate ads from “The Real Cost” anti-smoking campaign, a public education campaign aimed at reducing tobacco use among U.S. adolescents. Study 1 examines the relationship between self-reported recall of specific ads and anti-smoking belief endorsement in a nationally-representative sample of nonsmoking adolescents. To address limitations from Study 1, Study 2 evaluates the relationship between opportunities for exposure using Target Rating Points (TRPs), a measure of campaign reach and frequency, and anti-smoking belief endorsement in a nationally-representative sample of nonsmoking adolescents. Studies 3 and 4 employ functional magnetic resonance imaging (fMRI) to examine how anti-smoking ads are received and processed by the adolescent brain. Study 3 examines the relationships between ad-elicited neural response and subsequent ratings of perceived ad effectiveness and intention to share ads on social media in a sample of forty adolescent nonsmokers. Study 4 examines the moderating effect of ad-elicited brain response on the relationship between opportunities for campaign exposure and population-level ad recall. Analyses were conducted with a combined dataset representing: ad recall from a nationally-representative survey of adolescents; weekly, ad-specific TRPs; and ad-elicited neural response in brain regions implicated in social processing and memory encoding from a separate sample of adolescents. From the studies that comprise this dissertation, we can conclude the following: 1) opportunities for exposure and recalled exposure to campaign ads associate with endorsement of ad-targeted beliefs, suggesting the campaign has been effective through the theorized pathway of effects 2) ads that are perceived as more effective elicit greater response in brain regions implicated in social processing, and 3) ad-induced neural response in social processing and memory encoding brain regions partially explains the relationship between opportunities for ad exposure and recalled exposure. Findings suggest that neural measures of ad processing may be an important tool for forecasting which ads will be more effective in a target audience. These conclusions have important implications for the future design and implementation of mass media campaigns.