The Manchester native last year canceled a seven-date stretch of concerts in New York, with his manager citing "a mix of bizarre and rare" medical issues "connected to his throat, mouth/dental and respiratory system."
The manager, Pam Vander, did not reveal further details as she announced his death on Twitter but said a full statement would come later.
The famously temperamental singer was the only consistent member of The Fall but even with revolving lineups the band proved highly prolific, releasing its 32nd studio album last year.
While never finding -- or really seeking -- mainstream success, Smith's brashness and embrace of other art forms influenced a younger generation of indie bands such as Sonic Youth and Pavement.
Born to a working-class family, Smith's vocals often resembled the shouting of a pub patron but his lyricism was complex and abstract, delighting his loyal fan base which tried to decipher his words.
Memorable albums included "I am Kurious Oranj," an exploration set to a ballet of Dutch king William of Orange's ascension to the English throne in 1689.
1985's "This Nation's Saving Grace," which brought together both the dark flashes of punk and electronic elements, was often considered to be The Fall's greatest album.
The Fall -- named for Albert Camus' novel -- was once seen as a rival to Joy Division as the leading post-punk band in Manchester in the late 1970s, although Smith sarcastically described the band's genre as "country and northern."
While often marked by dark, intense guitar and dominant bass, The Fall's sound shifted as members fled.
Even his wife, the Greek DJ Elena Poulou, left as the keyboard player before the last album. A decade earlier, the couple created an album entirely with session musicians in Los Angeles after the rest of the band ditched them on a US tour.
Smith also earned a reputation for pithy quotes in his interviews. Among them:"I used to be a psychic, but I drank my way out of it."
