Sacajawea, a Shoshoni Native American, was born sometime in the late 18th century, probably around 1788 or 1789. When she was twelve years old, a Hidatsa raiding party captured her and took her away from her tribe. She was then sold or gambled into the possession of a French-Canadian fur-trader and trapper named Toussaint Charbonneau, who made her his wife. At the time, Charbonneau had another wife named Otter Woman, also a Native American.

In the winter of 1804-1805, the Lewis and Clark Expedition wintered at Fort Mandan. The Expedition was searching for a hypothesized Northwest Passage—a water-route linking the Atlantic and Pacific Oceans—and needed an interpreter of Indian languages in the Great Plains and Rocky Mountain regions they would be traveling. Thus they hired Charbonneau, and he brought Sacajawea along. While at Fort Mandan, Sacajawea (then around 16) gave birth to a boy named Jean Baptiste and nicknamed "Pomp" (Shoshoni for "First-Born"). Sacajawea would carry the infant with her for 8,000 miles over the course of the expedition, all the way to the Pacific and back. Soon everyone on the expedition grew to love the little boy.

Charbonneau, who at 46 was the oldest man on the expedition, was always causing problems, while his young Shoshoni wife was constantly solving them. Since the expedition had officially hired Charbonneau, and not Sacajawea, Sacajawea never received pay for her help. Nevertheless, she saved the expedition considerable trouble time and again. When Charbonneau's poor boatmanship in a storm nearly flipped one of Lewis and Clark's boats, causing many supplies to fall into the water, it was Sacajawea's quick thinking that saved the items, including scientific instruments, books, and journals. When it came time to barter with a group of Shoshoni for horses, not only could Sacajawea translate, but it turned out that the chief of the tribe was her long lost brother Cameahwait. As a result of Sacajawea's connections, the expedition received a generous number of horses. On the way back from the Pacific, Sacajawea led the explorers through the Bozeman Pass in the Rocky Mountains. Throughout the expedition, Sacajawea collected numerous roots and berries, helping to feed the men through difficult times. Perhaps most importantly, the presence of a Native American woman with a baby served as a sign to various Indian groups, especially the Nez Perce, that the Lewis and Clark Expedition was not a war party, and hence should not be attacked.

Despite the hardships she faced along the way, Sacajawea never complained throughout the grueling journey. At the end of the expedition, she was not paid, since she had never been formally hired. However, William Clark felt he owed her something and offered to raise and educate her son Jean Baptiste. Sacajawea and Charbonneau considered the offer and decided to turn their boy over to Clark; Jean Baptiste eventually went to Europe and learned four languages before returning to the United States to become a celebrated frontiersman.

According to traditional accounts, Sacajawea died in 1812 of a fever at Fort Manuel in South Dakota. The evidence that she died then is not perfect, however, and some historians claim that she actually left Charbonneau and returned to live with the Shoshoni, dying only in 1884.

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