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Born to Mendel and Sarah (née Fischgrund) in Munkacs, in the Bereg County of the Kingdom of Hungary (present-day Zakarpattia Oblast, Ukraine), in 1885, Gottesman emigrated to the United States as a child and later joined his father's paper-making business, M. Gottesman & Company, founded in 1886, in New York City. He went on to transform the firm into Central National-Gottesman Inc. Long after Gottesman's death, Central-National Gottesman became a multi-billion dollar corporation and the world's largest pulp and paper merchant. The firm grew through the acquisition of Lindenmeyr Paper Corporation, Perkins & Squire Company, D.F. Monroe and others.
He was also a successful banker, organizing the Central National Bank in New York City. Today, through a series of mergers, the bank became amalgamated into JPMorgan Chase & Co. Further, he became the director of the Eastern Corporation and of Rayonier Inc.
Gottesman became well known for his generous philanthropy. His monetary gifts extended to the New York Public Library and numerous Jewish organizations and institutions, including the D. Samuel Gottesman Library at Yeshiva University, Albert Einstein College of Medicine, in New York City.
One of his highest-profile gifts was the donation of the so-called Dead Sea Scrolls to the State of Israel, where they are housed in the Shrine of the Book. The shrine, located adjacent to the Israel Museum in western Jerusalem, was funded by a foundation established by Gottesman's children as a memorial to their father.
Samuel Gottesman was the uncle of billionaire David Gottesman.
His wife died of cancer in 1942 at age 49, a year after his granddaughter Jenifer was born. She likewise died of cancer, in 1991.
His daughter, Celeste Ruth Gottesman (1913–2013), was a wealthy modern-art collector and museum and library benefactor who resided in New York City. Her first husband was Jerome John Altman, whom she divorced in 1935 and then married American architect and philanthropist Armand Phillip Bartos. Celeste also established the Pinewood Foundation in 1958, named after her father's estate in Lawrence, Long Island, New York.