We live in an era of datafication, one in which life is increasingly quantified and transformed into intelligence for private or public benefit. When used responsibly, this offers new opportunities for public good. However, three key forms of asymmetry currently limit this potential, especially for already vulnerable and marginalized groups: data asymmetries, information asymmetries, and agency asymmetries. These asymmetries limit human potential, both in a practical and psychological sense, leading to feelings of disempowerment and eroding public trust in technology. Existing methods to limit asymmetries (e.g., consent) as well as some alternatives under consideration (data ownership, collective ownership, personal information management systems) have limitations to adequately address the challenges at hand. A new principle and practice of digital self-determination (DSD) is therefore required. DSD is based on existing concepts of self-determination, as articulated in sources as varied as Kantian philosophy and the 1966 International Covenant on Economic, Social and Cultural Rights. Updated for the digital age, DSD contains several key characteristics, including the fact that it has both an individual and collective dimension; is designed to especially benefit vulnerable and marginalized groups; and is context-specific (yet also enforceable). Operationalizing DSD in this (and other) contexts so as to maximize the potential of data while limiting its harms requires a number of steps. In particular, a responsible operationalization of DSD would consider four key prongs or categories of action: processes, people and organizations, policies, and products and technologies.