Sacagawea was born into a Lemhi ("Salmon Eater") tribe of Shoshone between Kenney Creek and Agency Creek, in Idaho. When she was about twelve years old, she and several other girls were kidnapped by a group of Hidatsa in a battle and was then taken to a Hidatsa village near the present-day Washburn, North Dakota. When she was about 13 years old, Sacajawea was either purchased or won while gambling by Toussaint Charbonneau, a French trapper living in the village, and became his second wife. Sacagawea was pregnant with her first child when the Corps of Discovery arrived near the Hidatsa villages to spend the winter of 1804-1805. Captains Meriwether Lewis and William Clark built Fort Mandan  and interviewed several trappers who might be able to translate or guide the expedition further up. They agreed to hire Charbonneau as an interpreter when they discovered his wife spoke the Shoshone language, as they knew they would need the help of the Shoshone tribes at the headwaters of the Missouri. Lewis recorded in his journal on November 4, 1804:

"a French man by Name Chabonah, who speaks the Big Belly language visit us, he wished to hire and informed us his 2 squars were snake Indians, we engage him to go on with us and take one his wives to interpret the Snake language…" [Meriwether Lewis]

Charbonneau and Sacajawea moved into the fort a week later. Lewis himself assisted at the birth of Jean Baptiste Charbonneau on February 11, 1805. In April, the expedition left Fort Mandan and headed up the Missouri River in pirogues. On May 14, 1805, Sacajawea rescued items that had fallen out of a capsized boat, including the journals and records that Lewis and Clark were keeping. The corps commanders, who praised her quick action on this occasion, would name the Sacajawea River in her honor. By August 1805 the corps had located a Shoshone tribe and was attempting to trade for horses to cross the Rocky Mountains. Sacajawea was brought in to translate, and it was discovered the tribe's chief was her brother, Cameahwait. Lewis recorded the reunion in his journal:

"Shortly after Capt. Clark arrived with the Interpreter Charbono, and the Indian woman, who proved to be a sister of the Chief Cameahwait. The meeting of those people was really affecting, particularly between Sah cah-gar-we-ah and an Indian woman, who had been taken prisoner at the same time with her, and who had afterwards escaped from the Minnetares and rejoined her nation" [Meriwether Lewis]

On 20 November,as the expedition approached the mouth of the Columbia River, Sacajawea gave up her beaded belt in order to allow the captains to trade for a fur robe they wished to return to President Jefferson. On the return trip, as they approached the Rocky Mountains in July of 1806, Sacajawea advised Clark to cross at what is now known as Bozeman Pass, later chosen as the optimal route for the Northern Pacific Railway to cross the continental divide. Charbonneau and Sacajawea spent three years among the Hidatsa after the expedition, before accepting William Clark's invitation to settle in St. Louis, Missouri in 1809. They entrusted Jean-Baptiste's education to Clark, who enrolled the young man in the Saint Louis Academy boarding school. Sacajawea gave birth to a daughter, Lisette, sometime after 1810. Some historical documents suggest Sacajawea died in 1812 of an unknown sickness. In a journal entry of the time, it was recorded that she "…had become sickly and longed to revisit her native country." The following year, John Luttig, a clerk at Fort Manuel Lisa recorded in his journal on December 20, 1812, that "…the wife of Charbonneau, a Snake Squaw [the common term used to denote Shoshone Indians], died of putrid fever, aged about 25 years leaving a fine infant girl".