The Mississippi River Restoration and Resilience Initiative Act creates a coordinated federal program to protect and restore the Mississippi River and its surrounding areas. The Environmental Protection Agency will establish a new National Program Office headed by a director who will oversee restoration projects across nine states: Arkansas, Illinois, Iowa, Kentucky, Louisiana, Minnesota, Mississippi, Missouri, Tennessee, and Wisconsin.

The program focuses on six main areas: improving water quality by reducing pollution and agricultural runoff, strengthening communities against flooding and storms, protecting fish and wildlife habitats, preventing invasive species, improving communication between organizations, and collecting scientific data. Projects can include restoring wetlands, removing dams or levees to restore natural water flow, protecting private land through conservation easements, cleaning up contaminated sites, and training workers for restoration jobs. The program will fund projects through federal grants and agreements with state agencies, local governments, tribes, nonprofits, and universities.

The law requires the EPA director to develop measurable goals within one year and a detailed action plan within two years, with updates every five years. It also establishes three research centers through the U.S. Geological Survey to study the Mississippi River and advise on restoration efforts. At least 5 percent of funding must go directly to Native American tribes. The federal government will typically cover 80 percent of project costs for non-tribal organizations, though it covers 100 percent for tribal projects and community capacity-building efforts. All projects must follow existing environmental laws and cannot duplicate work already being done by other federal programs.