- March 1: The Presbytery of Alabama was formed at Cahawba with 147 communicants in the state.
- March 6: Farrar Lodge No. 41 was chartered.
- June 11: The Grand Lodge of Alabama was established in Montgomery.
- November 9: Israel Pickens succeeded Thomas Bibb as governor.
- Elyton was founded and became the Jefferson County seat.
- St Clairsville became the county seat of St Clair County.
- August 31: John R. Gamble bought 100 acres of land, becoming the first settler near present-day Calera.
- Daniel Davis settled in Tuscaloosa County.
- German immigrant Peter Ingle was granted land on Mount Pinson.
- Robert Jemison, Jr came to Alabama with his parents.
- Warren Truss built a grist mill on the bank of the Cahaba River.
- Methodist minister Christopher Vandergrift and his family arrived near present-day Odenville.
In 1821, James Monroe was sworn in for his second term as President. Greece declared its liberation from the Ottoman Empire, beginning the Greek War of Independence. The United States took possession of its newly bought territory of Florida from Spain. Peru and Panama declared independence from Spain. Missouri was admitted as a state. Mexico gained its independence from Spain.
Notable births included mathematician Pafnuty Chebyshev, golfer Old Tom Morris, Bowery Boy William Poole, financier Jay Cooke, designer Louis Vuitton, pathologist Rudolf Virchow, writer Fyodor Dostoyevsky, writer Gustave Flaubert, and Red Cross founder Clara Barton. Notable deaths included Saint Elizabeth Ann Seton, poet John Keats, former emperor Napoleon of France, writer John William Polidori, and King Pōmare II of Tahiti.
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