IMPORTANCE: The negative effects of socioeconomic disadvantage on lifelong functioning are pronounced, with some evidence suggesting that these effects are mediated by changes in brain development. To our knowledge, no research has investigated whether parenting might buffer these negative effects. OBJECTIVE: To establish whether positive parenting behaviors moderate the effects of socioeconomic disadvantage on brain development and adaptive functioning in adolescents. DESIGN, SETTING, AND PARTICIPANTS: In this longitudinal study of adolescents from schools in Melbourne, Australia, data were collected at 3 assessments between 2004 and 2012. Data were analyzed between August 2016 and April 2017. EXPOSURES: Both family (parental income-to-needs, occupation, and education level) and neighborhood measures of socioeconomic disadvantage were assessed. Positive maternal parenting behaviors were observed during interactions in early adolescence. MAIN OUTCOMES AND MEASURES: Structural magnetic resonance imaging scans at 3 times (early, middle, and late adolescence) from ages 11 to 20 years. Global and academic functioning was assessed during late adolescence. We used linear mixed models to examine the effect of family and neighborhood socioeconomic disadvantage as well as the moderating effect of positive parenting on adolescent brain development. We used mediation models to examine whether brain developmental trajectories predicted functional outcomes during late adolescence. RESULTS: Of the included 166 adolescents, 86 (51.8%) were male. We found that neighborhood, but not family, socioeconomic disadvantage was associated with altered brain development from early (mean [SD] age, 12.79 [0.425] years) to late (mean [SD] age, 19.08 [0.460] years) adolescence, predominantly in the temporal lobes (temporal cortex: random field theory corrected; left amygdala: B, −0.237; P < .001; right amygdala: B, −0.209; P = .008). Additionally, positive parenting moderated the effects of neighborhood disadvantage on the development of dorsal frontal and lateral orbitofrontal cortices as well as the effects of family disadvantage on the development of the amygdala (occupation: B, 0.382; P = .004; income-to-needs: B, 27.741; P = .004), with some male-specific findings. The pattern of dorsal frontal cortical development in males from disadvantaged neighborhoods exposed to low maternal positivity predicted increased rates of school noncompletion (indirect effect, −0.018; SE, 0.01; 95% CI, −0.053 to −0.001). CONCLUSIONS AND RELEVANCE: Our findings highlight the importance of neighborhood disadvantage in influencing brain developmental trajectories. Further, to our knowledge, we present the first evidence that positive maternal parenting might ameliorate the negative effects of socioeconomic disadvantage on frontal lobe development (with implications for functioning) during adolescence. Results have relevance for designing interventions for children from socioeconomically disadvantaged backgrounds.