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Research has shown that prenatal maternal stress occurs commonly during pregnancy, and associated physical, psychological, and financial challenges are often compounded for African-American women from urban, low-income environments. The current study focused on a mindfulness-based intervention for a group of urban, low-income, pregnant African-American women. This randomized controlled pilot study involved a 2 × 3 mixed model design, comparing treatment as usual (TxAU) with the Mindful Motherhood intervention on several outcomes at pre-intervention, post-intervention, and one month post-intervention. A total of 65 adult participants (31 TxAU and 34 Mindful Motherhood) met the inclusion criteria and participated in the study. Due to significant attrition in both assessments and intervention participation, dose-effect analyses were employed to test treatment effects on outcome variables with multiple linear regressions. Preliminary findings support the efficacy of the Mindful Motherhood training in improving levels of mindfulness, reducing reactive cortisol response, and reducing pregnancy-related stress at post-intervention and improving pregnancy-related positive experience and reducing depressive symptoms at one month follow-up. However, none of these effects appeared to have lasting impact on the participants, and treatment did not appear to impact perceived stress or baseline salivary cortisol levels. This pilot study is believed to be the first empirical research on a mindfulness-based intervention with a group of urban, low-income, pregnant African-American women. These preliminary results support the efficacy of mindfulness-based interventions with this minority population and encourage efforts to optimize recruitment and retention of underprivileged participants.