He was born as Bernhard Valvrojenski on 26 June 1865, in Butrimonys, Southern Lithuania, to Albert (originally Alter) Valvrojenski, a poor but well-read lumber merchant, and his wife Julia (originally Eudice) Mickleshanski.

He was the eldest son in the family and his parents had high hopes from him. His family immigrated to Boston from Lithuania in 1875, changing their family name to "Berenson." Bernard was a Jew by birth, but later on converted to Christianity.

He attended Harvard University where he studied under Charles Eliot Norton and earned his B.A. in 1887. He was a bright student and tutored some of his classmates including George Santayana who eventually became a cultural philosopher.

He then moved to Oxford, England where he became acquainted with the art collector Edward Perry "Ned" Warren. He also met Renaissance scholar, Herbert Horne who influenced the young Bernard a lot.

After meeting the famous connoisseur Giovanni Cavalcasselle in 1889, he started publishing various studies on art. He had read several of the works of the Italian art historian Giovanni Morelli and was deeply influenced by him, and this was reflected in his writings.

By 1890 he also began dealing in art, and scouted pictures for his art historian friend Jean Paul Richter, collector Edward Perry "Ned" Warren, and the London dealer Otto Gutekunst.

In 1892, he acquired his first work as a dealer and helped the British collector James Burke obtain some Impressionist works and a painting of Piero di Cosimo.

His book on Renaissance art titled ‘The Venetian Painters of the Renaissance with an Index to their Works’ was out in 1894. His knowledge of art combined with his systematic approach was well appreciated.

In 1895, he published ‘Lorenzo Lotto, an Essay on Constructive Art Criticism’ which won the praises of art critics, especially Heinrich Wolfflin. The very next year he brought out ‘The Florentine Painters of the Renaissance’ which was again lauded for its innovative interpretation of art. Another book ‘The Central Italian Painters of the Renaissance’ was published in quick succession in 1897.

During the late 1890s he started working on what would eventually become his masterpiece—‘The Drawings of the Florentine Painters’—which was published in 1903 after six years of research and hard work.

His book ‘The North Italian Painters of the Renaissance’ was published in 1907. In this book he discussed his distaste for Modern Art and gave a judgment of Mannerist Art which kindled some controversy.

Over the course of his writing career he also published two volumes of journals, ‘Rumor and Reflection’ and ‘Sunset and Twilight’. He also wrote some other books including ‘Aesthetics and History’ and ‘Sketch for a Self-portrait’.

He was much respected for his knowledge of Renaissance art and was considered an authority on the subject. He served as a consultant to several major art collectors and earned a lot of wealth acting in this position.

Even though he had not received any formal education in art history, he was awarded two honorary degrees by the University of Florence and University of Paris in 1955.

In 1888 he met Mary Smith, an art historian, on his trip to England. He fell in love with her despite her being married to the British politician, Frank Costelloe. She too reciprocated his feelings and left her husband and two small children to live with Berenson.

He married Mary after her first husband died in 1900. After a few years Mary fell in love with another man, and in retaliation, Berenson too started having affairs with other women including Belle da Costa Greene, Baroness Gabrielle La Caze, and Elisabetta "Nicky" Mariano.

He died on 6 October, 1959 at the age of 94 after having lived a long and productive life.