The auctioneers said Lennon played the guitar, which is expected to exceed its estimate of $US600,000 to $US800,000 ($A925,000 to $A1.2m), on the Beatles' 1965 album Help!.
The guitar was lying in an attic and was rediscovered by the current owners during a house move.
The founders of US-based Julien's Auctions said they travelled to Britain to verify the guitar and found the original case - a Maton Australian-made guitar case - in the trash.
Martin Nolan, executive director and co-founder of Julien's Auctions, told Reuters the owners knew they had the instrument at one point, but thought it had been lost.
The guitar is believed to have ended up in their hands through British musician Gordon Waller, a member of the 1960s pop duo Peter and Gordon.
"Gordon was gifted it from John Lennon, then Gordon gifted it to his road manager, and that's where the guitar stayed for all these years," Nolan said.
The guitar will be auctioned on May 29 at the Hard Rock Cafe in New York and on the auctioneer's website.
Earlier this year, a stolen Hofner bass guitar belonging to Paul McCartney was found and returned to Lennon's fellow Beatle after 51 years following a global hunt.
Musical instruments belonging to prominent members of the Beatles have fetched a high price at previous auction.
In 2015, a guitar stolen from Lennon in the 1960s sold for $US2.41 million ($A3.72 million) at an auction in California.Â
