While debate continues about the details, many historians believe that Sacagawea was born near present-day Lemhi, Idaho in circa 1786. She was a member of the Lemhi band of Shoshoni Indians but circa 1800 she was captured by a party of Hidatsa (Minitari) Indians and taken to their village in the region of the upper Missouri River in present-day North Dakota. The Hidatsa people may have given her the name Sacagawea derived from the Hidatsa words for "bird" and "woman."

She was later sold (or perhaps won in a gamble) to a French Canadian fur trapper named Toussaint Charbonneau who married her in 1804. Later that year the Lewis and Clark expedition arrived in the region on their way to the Pacific Coast and hired Charbonneau as a guide and interpreter. While they disliked Charbonneau, they knew that his wife could speak Minitari, French, and Shoshoni. This would prove valuable later when they needed to get horses from her Shoshoni tribe, known for their horsemen, in order to make the crossing over the Rockies.

Sacagawea proved to be a significant asset in other ways. She identified plants for the explorers and searched for edible fruits and vegetables to supplement their diet. When a boat was tipped over, she rescued the journals, medicines, and other valuables that had washed overboard. Her strength in the face of hazards and deprivations later became legendary.

Sacagawea and Charbonneau remained with the expedition to the coast of Oregon and helped the explorers to communicate with the various peoples of the Plains and the Northwest. The party spent a long and wet winter in the general vicinity of the mouth of the Columbia River in Oregon before returning east. On the return journey Sacagawea and Charbonneau remained with the Mandan Indians in present-day North Dakota while the rest of the group continued to St. Louis, Missouri.

The fate of Sacagawea after parting with the expedition is less clear. There is evidence that Sacagawea and Charbonneau traveled to St. Louis in 1809 to leave their son to be educated by William Clark of the expedition. According to contemporary sources, a woman identified as Charbonneau's wife and believed to be Sacagawea died in 1812 at Fort Manuel, in present-day South Dakota. Some biographers speculate, however, that the woman who died at Fort Manuel was Charbonneau's other wife and that Sacagawea eventually rejoined the Shoshoni people at the Wind River reservation in Wyoming and died there in 1884.

Commemorating the bicentennial of the 1804-1806 expedition, celebrations began in 2004 in cities and historic sites along the Corps of Discovery's route.