The physicist gifted the holy book in 1932 to Harriet Hamilton, a temporary secretary of his wife Elsa, the auction house claims.
Einstein wrote on a blank page in German: "This book is an inexhaustible source of living wisdom and consolation.
"Read therein and think thereon. A. Einstein."
One of the world's most famous scientists, Einstein was often asked to make public pronouncements about God and religion.
Cassandra Hatton, senior specialist in Sotheby's books and manuscripts department told financial news site Barron's: "We're thrilled to be offering the only bible signed and inscribed by Albert Einstein to ever come to auction.
"This alone is a rare and exciting moment, but what is even more compelling is Einstein's inscription."
Hattan added that the inscription is likely to spark new debates about Einstein's beliefs.
The Bible is expected to get between $200,000 and US$300,000.
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