Purpose: To assess the relationship between youth’s exposure to the Food and Drug Administration’s national tobacco public education campaign, The Real Cost, and changes in campaign-targeted beliefs. Design: Longitudinal design with baseline survey and 2 postcampaign follow-up surveys. Sample: Youth from 75 US media markets (N = 1680) who completed all 3 surveys and had experimented with or were susceptible to future cigarette smoking. Measures: Exposure was measured by self-reported frequency of ad exposure and media market–level target rating points. Agreement with 30 self-reported tobacco-related beliefs was assessed in 3 categories: (1) beliefs specifically targeted by campaign messages (campaign-targeted belief), (2) beliefs not targeted by the campaign (nontargeted beliefs), and (3) beliefs corresponding to other media campaigns on air concurrent with The Real Cost (ambiguous beliefs). Analysis: Descriptive analyses of aggregate changes in beliefs and logistic regressions to examine the association between campaign exposure and beliefs. Intervention: The Real Cost. Results: Agreement with campaign-targeted beliefs increased from baseline to first and second follow-ups, with a mean relative increase of 10.4% and 11.5%, respectively. Nontargeted beliefs did not change substantially. Both measures of campaign exposure were positively associated with increased odds of agreeing with 5 of 8 campaign-targeted beliefs. Exposure was not significantly associated with 12 of 14 nontargeted tobacco-related beliefs. Discussion: A sustained national tobacco public education campaign can change population-level perceptions of tobacco-related harms among youth.