The Ross Sea, which is considered to be one of the world's most ecologically important oceans, will host the marine park. It will cover a massive 1.55 million square km of ocean and be protected from commercial fishing.
The European Union and 24 countries on Friday signed an agreement to create the world's largest marine park in the Ross Sea in the Antarctic Ocean.
Scientists and activists described the agreement as a historic milestone in global efforts to protect marine diversity.
They also said the marine park will also allow for a greater understanding of the impact of climate change.
"The Ross Sea Region Marine Protected Area will safeguard one of the last unspoiled ocean wilderness areas on the planet – home to unparalleled marine bio-diversity and thriving communities of penguins, seals, whales, seabirds, and fish," US Secretary of State John Kerry said in a statement.
The Ross Sea is considered to be one of the world's most ecologically important oceans.
The marine park will be protected from commercial fishing for 35 years, the Commission for the Conservation of Antarctic Marine Living Resources said, after a meeting in Hobart, Australia.
The sanctuary will cover more than 12 percent of the Southern Ocean, a massive 1.55 million square km (600,000 square miles), which is home to more than 10,000 species, including most of the world's penguins, whales, seabirds, colossal squid and Antarctic tooth fish.
Fishing will be completely banned in 1.1 million square km (425,000 square miles) of the Ross Sea, while some fishing for krill and sawfish will be allowed in certain areas designated for research.
Russia agreed to the deal, after blocking conservation proposals on five previous occasions.
The 25-member commission, which includes Russia, China, the United States and the European Union, requires unanimous support for decisions.
"They all have diverse economic, political interests, and to get them all to align - especially in the context of their divergent economic interests - is quite a challenge," Evan Bloom, director at the US Department of State and leader of the US delegation.