The objective of this study was to perform a systematic review to examine the effectiveness of tobacco dependence education versus usual or no tobacco dependence education on entry-level health professional student practice and client smoking cessation. Sixteen published databases, seven grey literature databases/websites, publishers’ websites, books, and pertinent reference lists were searched. Studies from 16 health professional programs yielded 28 RCTs with data on 4343 healthcare students and 3122 patients. Two researchers independently assessed articles and abstracted data about student knowledge, self-efficacy, performance of tobacco cessation interventions, and patient smoking cessation. All forms of tobacco were included. We did not find separate interventions for different kinds of tobacco such as pipes or flavoured tobacco. We computed effect sizes using a random-effects model and applied meta-analytic procedures to 13 RCTs that provided data for meta-analysis. Students’ counseling skills increased significantly following the 5As model (SMD = 1.03; 95% CI 0.07, 1.98; p < 0.00001, I2 94%; p = 0.04) or motivational interviewing approach (SMD = 0.90, 95% CI 0.59, 1.21; p = 0.68, I2 0%; p < 0.00001). With tobacco dependence counseling, 78 more patients per 1000 (than control) reported quitting at 6 months (OR 2.02; 95% CI 1.49, 2.74, I2 = 0%, p = 0.76; p < 0.00001), although the strength of evidence was moderate or low. Student tobacco cessation counseling improved guided by the above models, active learning strategies, and practice with standardized patients.