Purpose: Depression and impulsivity have been positively correlated to problem gambling, but no study has focused on their combined effects on the onset of problem gambling. This study examined the possible synergistic effect of depressive symptoms and impulsivity in early adolescence on late adolescence gambling behaviors among a longitudinal cohort of 678 students from Baltimore, Maryland. Methods: The South Oaks Gambling Screen-Revised for Adolescents, Teacher Observation of Classroom Adaptation-Revised, and Baltimore How I Feel-Adolescent Version, were used to assess late adolescence gambling behaviors, early adolescence impulsivity, and depressive symptoms, respectively. Data analyses were conducted using analysis of variance and binary logistic regression models. Results: Problem gamblers (PGs) were 12% of the sample (includes at-risk and PGs), 87.5% of whom were males and 12.5% were females (p < .001). Among males, there appeared to be a slight association between early adolescence depressive symptoms and late adolescence problem gambling. Compared with nongamblers and social gamblers, depressive symptoms increased the odds of problem gambling by four-fold (PGs vs. nongamblers: OR = 4.1, 95% CI = .73–22.47, p = .11; PGs vs. social gamblers: OR = 3.9, 95% CI = .78–19.31, p = .10). Among those with high depressive symptoms, increases in impulsivity decreased the odds of problem gambling while among those with high impulsivity, increases in depressive symptoms decreased the odds of problem gambling. Conclusions: Early adolescence depressive symptoms appear to be more positively associated with late adolescence problem gambling than early adolescence impulsivity, there seems to be a divisive interaction between depressive symptoms and impulsivity on problem gambling.