To evaluate the efficacy of the Social ABCs parent‐mediated intervention for toddlers with suspected or confirmed autism spectrum disorder (ASD), through a cross‐site randomized control trial, sixty‐three parent–toddler dyads (toddler age: 16–30 months) were randomized into treatment (Social ABCs) or control (service‐as‐usual) conditions. Video data were obtained at three key time‐points: Baseline; Post‐training (PT; week 12); and Follow‐Up (week 24). Analyses included 62 dyads. Treatment allocation significantly accounted for PT gains, all favouring the Treatment group, in (1) child functional vocal responsiveness to parent prompts (R2 = 0.43, P < .001), (2) child vocal initiations (R2 = 0.28, P < .001), (3) parent smiling (R2 = 0.09, P = .017), and (4) fidelity of implementation (R2 = 0.71, P < .001). A trend was observed for increased social orienting (R2 = 0.06, P = 0.054); gains in parent smiling significantly predicted increases in child smiling and social orienting. Parents in the treatment condition reported significant gains in self‐efficacy following the intervention (P = 0.009). No differential effects emerged for performance on standardized measures. The Social ABCs is a relatively low‐resource, efficacious intervention, with potential to be a cost‐effective means of intervening at the first signs of possible ASD. Autism Res 2017, 10: 1700–1711. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Clinical Trial Title: Social ABCs for Toddlers with Signs of Autism Spectrum Disorder: RCT of a Parent‐Mediated Intervention http//ClinicalTrials.gov identifier: NCT02428452.