The following events occurred in the 1800s (1800 – 1809):
- The Corps of Discovery, led by Meriwether Lewis and William Clark, begins its expedition to the Pacific Northwest, guided in part by the Shoshone Sacagawea.
- Baron John Jacob Astor exploits castor in the northwest.
- Vice President Aaron Burr's alleged sedition against the United States is exposed by General James Wilkinson, actually Burr's partner.
- June 13 – Lewis sees the mountains of Twin Peaks to the north and the expedition heads toward the region after Missoula.
- c. September 17 – Lewis and Clark split their company to gather provisions.
- September 18 – The Nez Perce send most of their men to war.
- September 20 – Clark makes contact with the Nez Perce soon after crossing the present-day eastern border of Washington.
- September 21 – Clark and his men visit another settlement down river and meet Twisted Hair, the Nez Perce chief. They are given a map of the area showing White Tail Falls. Clark sends Reuben Fields to find Lewis' company and guide them to the camp.
- September 25 – Lewis writes to President Jefferson about a sacred place where Twisted Hair told him several white men lived, and three bizarre artifacts the chief says they gave him. One of them is a jade ring. Lewis resolves to take a group of men to find the place the chief described.
- c. September 28 – Lewis travels with a small band to the place Twisted Hair mentioned and has a bizarre experience, writing a fragmented dispatch about a "silent man," lights in the sky, the color red, and classical statuary. After returning, he destroys the map. His dispatch to President Jefferson leads the president to believe Lewis is delirious.
- October 3 – Lewis reunites with Clark. In his next dispatch, he mentions that the men who accompanied him have no memory of what happened above the falls and that he intends to keep Twisted Hair's ring.
- The Corps of Discovery arrives back in St. Louis after reaching the Pacific Ocean. President Jefferson pens a journal entry about Lewis' experience.
- The Corps of Discovery, including Lewis and Clark, arrive in Washington, D.C. to a heroes' welcome. President Jefferson appoints Lewis governor of the Upper Louisiana Territory as reward for his service, replacing James Wilkinson.
- Aaron Burr is arrested and set on trial.
- September 21 – Lewis announces in his Missouri Gazette the founding of the St. Louis Masonic Lodge, Lodge III, with him as its first Master.
- October 10 – En route to Washington, D.C. on a secret mission, Meriwether Lewis arrives at Grinder's Stand along the Natchez Trace in Tennessee. Priscilla Grinder recounts him ranting about his enemies following him and notices him fiddling with a leather pouch hung around his neck.
- October 11 –
- At three in the morning, Mrs. Grinder awakens to the sounds of a struggle and later finds Lewis dead, shot twice and stabbed repeatedly. His death is ruled a suicide.
- Lewis' escort Major James Neely arrives at midday, nearly twelve hours after Lewis' death, to confiscate Lewis' belongings and supervise his burial near Grinder's Stand.
- October 18 – Over a week after Lewis' death, Major Neely writes to Thomas Jefferson from Nashville to report what has happened. He dispatches Thomas Freeman to escort Lewis' possessions to Monticello.
- In the following weeks, Major Gilbert Russell writes to Jefferson attesting that in the weeks before his death, Lewis had been strong-minded and purposeful, and that his death had been an act of murder, not suicide.
- End of November – Freeman arrives at Monticello with Lewis' belongings, where Isaac Coles takes inventory. Many are unaccounted for or observed to have been taken by James Neely, including his cash, expedition journals, weapons, horses, and the small leather pouch.