- January 25: A deadly tornado struck Fultondale and Center Point.
- February 20: 2021 Cullman County plane crash
- April 12–14: The Frontier Conference 2021, originally scheduled for April 2020, was held at the Lyric Theatre.
- June 18–20: The Euphonious music festival was held at the Birmingham Zoo.
- September 24–26: Furnace Fest 2021
- 1st quarter: SouthFirst Bank of Sylacauga merged with FirstBanc of Talladega.
- February: Tuscaloosa's University Boulevard Hooligans relocated to 15th Street.
- Heiche opened an advanced metal coating facility at the Jasper Industrial Park.
- January 6: Cook Out opened at 2411 3rd Avenue South.
- January 25: Buc-ee's opened in Leeds.
- February: Alexander Shunnarah and Tyler Vail founded Shunnarah Vail Trial Attorneys.
- January: My Supply Chain Group was acquired by NTT DATA Business Solutions of Bielefeld, Germany.
- January: Magnolia Meadows Golf Course in Columbiana closed.
- February: Moe's Southwest Grill at Vestavia Hills City Center closed.
- February 20: Tuscaloosa's Ruan Thai restaurant closed.
- February 28: Catfish Cabin in Albertville closed.
- February: The Plainsman transitioned to an online publication.
- March 1: Cabaniss, Johnston, Gardner, Dumas & O'Neal was acquired by Phelps Dunbar of New Orleans, Louisiana.
- January 26: 2021 Birmingham Board of Education special election
- February 2: The 2021 Alabama legislative session began.
- February: Birmingham's Mayor’s Office of Sports and Entertainment was merged into the Birmingham Department of Innovation and Economic Opportunity.
- August 24: 2021 Birmingham municipal election
- Chuck Holmes became executive director of the Alabama Humanities Alliance.
- January 11: Cornell Wesley began his term as head of the Birmingham Department of Innovation and Economic Opportunity.
- February: Chad Carson was named permanent dean of the Brock School of Business at Samford University.
- John Owen retired as chief operating officer of Regions Bank.
- Photographer Joe Songer retired from al.com.
- January 1: Mike Coppage, former Birmingham Police chief and Alabama Department of Public Safety director
- January 3: Bill Stewart, professor of political science
- January 3: Joann Bashinsky, Golden Flake heiress
- January 10: Derrick Johnson, Huffman High School coach
- January 10: Corbin Day, chair of Jemison Investment Company
- January 16: Scotty McCallum, UAB president and Vestavia Hills mayor
- January 16: Leon Edwards, Edwards Chevrolet president
- January 20: Sonny Penhale, Helena mayor
- January 21: Marc Phillips, musician and music minister
- January 28: Sammy Wilson, Clanton city council
- February 2: Danny Ray, emcee and "cape man" for James Brown
- February 15: Jimmy Evans, former Attorney General of Alabama
- March: Kevin Turner, UAB Gospel Choir director
- The Wife Upstairs, novel by Rachel Hawkins
- Shaking the Gates of Hell, family memoir by John Archibald
- Asian Passage at the Birmingham Zoo
- Birmingham VA Mental Health Clinic on Crestwood Boulevard
- Buc-ee's travel stop in Leeds
- The Citizen "micro-unit" apartments on 18th Street South
- Cortland Vesta Apartments on Highland Avenue
- Hilton Tapestry Collection in Homewood
- Hoover Fire Station No. 11 in Trace Crossings
- Jones Valley Trail extension to Avondale
- Motion Industries area fluid power shop, hose & rubber shop, and engineering department
- Protective Stadium at the BJCC
- The Railyard "micro-unit" apartments on 1st Avenue South
- Tarrant City Hall
- The Birmingham Police Real Time Crime Center on the 4th floor of Birmingham Police Headquarters
- Malone Roofing building at 2689 Queenstown Road in Irondale.
In 2021 insurrectionists stormed the U.S. Capitol, disrupting Congress's certification of the 2020 presidential election. For inciting the mob, President Trump was impeached for a second time.
Notable people who died in 2021 included activist Vernon Jordan; actors Hal Holbrook, Cloris Leachman, Christopher Plummer, and Cicely Tyson; baseball hall of famers Hank Aaron and Don Sutton; basketball coach John Chaney; director Robert Altman; football coach Marty Schottenheimer; magician Mark Wilson; musician Mary Wilson; poet Lawrence Ferlinghetti; radio/television interviewer Larry King; radio host Rush Limbaugh; and former Secretary of State George Schultz.
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