Background: Physical activity exerts cancer-protective effects, yet most Americans are inactive, especially in the South, where cancer incidence rates are generally higher. Telephone-based approaches can help overcome physical activity intervention barriers in this region (literacy, costs, lack of transportation/technology, distance from facilities) and can be automated via interactive voice response (IVR) systems for improved reach and cost-effectiveness. Aims: To evaluate the Deep South IVR-supported Active Lifestyle (DIAL) intervention. Method: A pilot randomized controlled trial was conducted among 63 underactive adults in Birmingham, Alabama, from 2015 to 2017. Results: Retention was 88.9% at 12 weeks, and =75% adherence (IVR contact on at least 63 out of 84 days) was noted among 62.5% of intervention participants. Intervention participants reported larger increases in self-reported minutes of moderate-to-vigorous intensity physical activity from baseline to 12 weeks than the wait-list control arm (median change = 47.5 vs. 5.0 minutes, respectively, p = 0.09). Moreover, the intervention produced significantly greater increases in physical activity self-regulation (p < 0.001) and social support from family (p = 0.001) and friends (p = 0.009) from baseline to 12 weeks, compared with the wait-list control. Significant decreases in self-reported sleep disturbance also were found in the intervention arm but not among the controls, p < 0.05. Overall, intervention participants reported being satisfied with the DIAL program (71.4%) and would recommend it to friends (92.9%). Discussion: Findings support the feasibility, acceptability, and preliminary efficacy of the DIAL intervention. Conclusion: Next steps include intervention refinement in preparation for a fully powered efficacy trial and eventual dissemination to rural counties.