The letter, signed by Gandhi and dated 6 April 1926, was written to Milton Newberry Frantz, a religious elder in the US at the time.
Gandhi wrote that Jesus was "one of the greatest teachers of mankind".
The letter has been in a private collection for decades and is being sold by the Pennsylvania-based Raab Collection for $50,000 (£36,275).
Gandhi, an iconic independence leader, is revered in India and fondly known as father of the nation. He was a Hindu, who wrote extensively about the religion's philosophy and teachings.
Gandhi wrote to Frantz from his residence in the Sabarmati ashram in the western state of Gujarat in response to a letter asking him to read a publication about Christianity.
Gandhi wrote: "Dear Friend, I have your letter. I am afraid it is not possible for me to subscribe to the creed you have sent me. The subscriber is made to believe that the highest manifestation of the unseen reality was Jesus Christ. In spite of all my efforts, I have not been able to feel the truth of that statement."
Gandhi wrote that Jesus was 'one of the greatest teachers of mankind'
"I have not been able to move beyond the belief that Jesus was one of the great teachers of mankind. Do you not think that religious unity is to be had not by a mechanical subscription to a common creed but by all respecting the creed of each?"
The Raab Collection said in a statement that their "research discloses no other letter of Gandhi mentioning Jesus to have ever reached the public market."
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