A spokeswoman for Memorial Medical Center in Lufkin, Texas, said Wilson, 76, was pronounced dead in the emergency room after complaining of difficulty breathing during a meeting with a friend, CNN reported.
Wilson, a 12-term congressman from Texas' 2nd Congressional District from 1973 to 1997, inspired the book and movie "Charlie Wilson's War," which told of his campaign to supply weapons to Afghan mujahedeen fighters battling Soviet invaders.
Wilson had undergone a heart transplant in 2007 and returned to Lufkin afterwards, the U.S. broadcaster said.
The book was written by George Crille and Wilson was portrayed by Tom Hanks in the 2007 movie.
"Hanks did a great job," Wilson told CNN in 2008.
CNN said Wilson, a U.S. Naval Academy graduate and Navy veteran, was first elected to Congress in 1972 and gained fame for his fondness for the high life, earning him the nickname "Good Time Charlie." His efforts to build international support for the Afghan rebels was credited with helping them gain the upper hand over the Soviet Union.