In an attempt to protect pristine coral reefs, rare fish and underwater volcanoes, Mr Bush will mark out an area spanning 195,000 square miles in the Pacific Ocean as a trio of "marine national monuments," a spokesman said.
The areas include the Mariana Trench and northern Mariana Islands, the Rose Atoll in American Samoa and a chain of remote islands in the Central Pacific.
Fishing will be barred or limited in many island areas while the 21 volcanoes and hydrothermal vents along the ocean floor beneath the Mariana Islands will also be protected.
"This is very, very big," James Connaughton, chairman of the White House Council on Environmental Quality Issues, said.
"In the last several years, it's on par with what we've been able to accomplish on land over the course of the last 100 years," he said, noting that the total area would "comprise the largest areas of ocean or ocean seabed set aside as marine protected areas in the world."
Collectively, the three areas will nudge out the Phoenix Island Protected Area, established in 2008 by the South Pacific nation of Kiribati as the world's largest protected area.
They also top Mr Bush's last such announcement of a marine protection area in 2006 - the 140,000 square miles (363,000 square kilometers) of Pacific Ocean near the northwestern Hawaiian islands.
"Because these areas are pristine it gives us the best opportunity to understand effects in the ocean system," said Mr Connaughton.
In some island areas, commercial fishing will be prohibited within 50 nautical miles while indigenous, recreational or research fishing will be permitted on a case-by-case basis, he said.
The move was praised by environmentalists, though details remained unclear on the degree of protection the areas will be afforded.
For scientists, the designations are "wonderful opportunities," said Roger McManus, vice president for global marine programs at the environmental group Conservation International.
"You don't get a better natural laboratory than we have in these places," he said.