DNA-Based population screening in the United States has the promise to improve the health of all people in all communities. We highlight recent DNA-based population screening examples at the state, local, and individual level. Key public health principles and concepts with a focus on equity appear to be lacking in current efforts. We request 'A Call to Action' that involves all partners in DNA-based population screening. Potential actions to consider include: a) identification and elimination of systemic barriers that result in health inequities in DNA-based population screening and follow-up; b) creation of a national multidisciplinary advisory committee with representation from underserved communities; c) revisiting well-described public health screening principles and frameworks to guide new screening decisions and initiatives; d) inclusion of the updated Ten Essential Public Health Services with equity at the core in efforts at the local, state and national level.