The sanctuary program was intended to be an integrated, complementary system of marine parks. This important identity was first realized in 1981 with the addition of three new sites: Gray's Reef, Looe Key, and Gulf of the Farallones National Marine Sanctuaries. These sites have embarked on ambitious efforts to protect their resources.

For example, the Gulf of the Farallones National Marine Sanctuary's Sanctuary Education Awareness and Long Term Stewardship (SEALS) program recruited volunteers to help protect pupping harbor seals; by 2005 the number of seal pups at the SEALS observation sites had increased, reversing an alarming decline for the first time in 15 years. In a more recent effort, the sanctuary developed the White Shark Stewardship Project to protect and conserve the eastern Pacific white shark population. The Gray’s Reef National Marine Sanctuary updated its regulations, including a ban on spear fishing (2010), and established a research only area in 2011 to help scientists assess the impacts of human and natural events both within and outside the sanctuary.