The hijacking of Southern Airways Flight 49 started on November 10, 1972 in Birmingham, Alabama, stretching over 30 hours, three countries, and 4,000 miles (6,400 km), not ending until the next evening in Havana, Cuba. Three men, Melvin Cale, Louis Moore, and Henry D. Jackson Jr. successfully hijacked a Southern Airways Douglas DC-9 that was scheduled to fly from Memphis, Tennessee to Miami, Florida via Birmingham and Montgomery, Alabama and Orlando, Florida. The three were each facing criminal charges for unrelated incidents. 34 people, including 31 passengers and 3 crew members, were aboard the airplane when it was hijacked. The hijackers' threat to crash the aircraft into a nuclear reactor led directly to the requirement that U.S. airline passengers be physically screened, beginning January 5, 1973.

Southern Airways (IATA: SO, ICAO: SOU, Call sign: Southern) was an airline (known at the time as a "local-service air carrier" as designated by the federal Civil Aeronautics Board) in the United States, from its founding by Frank Hulse in 1949 until 1979, when it merged with North Central Airlines to become Republic Airlines. Southern's corporate headquarters were in Birmingham, with operations headquartered at Hartsfield–Jackson Atlanta International Airport, near Atlanta.