Cancer is one of the most important societal challenges in the world, with over 23 million new cases/year and 10 million deaths/year, that will only be properly tackled with a stronger focus on prevention. This calls for an informed population, aware of risk factors and willing to adopt preventive behaviors and early cancer screenings. For that purpose, 2' Life-changing minutes was created, the first ever televised Entertainment-Education series on cancer prevention. This study aims to evaluate the impact of 2' Life-changing minutes, a novel E-E format for cancer prevention, on knowledge gains and behavior changes. Two complementary studies were performed involving a total of 1314 participants: a test-screening (TS) study targeting potential viewers of the series, and a natural-screening (NS) study targeting those that spontaneously watched the series on television. We found (i) very high levels of appreciation and narrative engagement, and also willingness to see more episodes; (ii) statistically significant knowledge gains, ranging from 17% to 44%, on all four topics tested; (iii) evidence of effective behavior change. Regression analysis showed that narrative engagement was the best predictor of behavior change [NS: odds ratio (OR) = 3.38, 95% confidence interval (CI) = 1.70-6.74, p = 0.001; TS: OR = 2.05, 95% CI = 1.13-0.371, p = 0.018]. This study demonstrates the series' real impact and serves as a proof-of-concept for a novel strategy of cancer prevention that is based around compelling health narratives, rather than information or data, to engage viewers, increase knowledge and induce behavior change.