[1] The first inhabitants of the region were indigenous people who began using the waters of southeastern Lake Ontario for transportation and trade in canoes and other small boats in prehistoric times.

[6] Over many centuries, these indigenous peoples developed a deep and lasting understanding of and bond with Lake Ontario and its fish and wildlife.

[4] Scuba divers and shipwreck explorers have identified 41 shipwrecks and the wreckage of one aircraft within the boundaries of the Lake Ontario National Marine Sanctuary which together span more than 200 years of the history of the United States, including the role of Lake Ontario in supporting the growth of the industrial core of the early United States.

[6] The wreck of the 135-foot (41 m) three-masted schooner St. Peter, which operated from 1873 until she sank in a storm in 1898, sits upright in 117 feet (36 m) of water on the lake bottom northeast of Pultneyville, New York; it is one of the most accessible shipwrecks for recreational divers in the sanctuary and is listed on the National Register of Historic Places.

[6] The sanctuary also may contain several other underwater archaeological sites related to the region's maritime history in addition to the wrecks, such as the remnants of shipwrecks, piers, and navigational aids.

[9] The governor of New York, the Onandaga Nation, and several historical societies, museums, and recreation, conservation, tourism, and education groups endorsed the nomination.

However, the commercial shipping community and several United States Government agencies expressed safety concerns about including a portion of the St. Lawrence River in the proposed sanctuary.

[3] After a mandatory wait for 45 days of continuous session of the United States Congress, beginning on the date the final rule was published,[1][4] NOAA designated the sanctuary on September 6, 2024.

[6] In addition to their historical value, the sanctuary's shipwrecks, aircraft wreck, and other submerged archaeological sites offer recreational diving opportunities.