Matthiessen was born in Pasadena, California on February 19, 1902.
He was the fourth of four children born to Frederick William Matthiessen (1868–1948) and Lucy Orne Pratt (1866).
The family's three older siblings included Frederick William (1894), George Dwight (1897) and Lucy Orne (1898).

In Pasadena he was a student at Polytechnic School.
Following the separation of his parents, he relocated with his mother to his paternal grandparents home in LaSalle, Illinois.
His grandfather, Frederick William Matthiessen, was an industrial leader in zinc production and a successful manufacturer of clocks and machine tools.
He also served as mayor of Lasalle for ten years.
The grandson completed his secondary education at Hackley School, in Tarrytown, New York.

In 1923, Matthiessen graduated from Yale University, where he was managing editor of the Yale Daily News, editor of the Yale Literary Magazine and a member of Skull and Bones.
As the recipient of the university's Deforest Prize, he titled his oration, "Servants of the Devil", in which he proclaimed Yale's administration to be an "autocracy, ruled by a Corporation out of touch with college life and allied with big business".
In his final year as a Yale undergraduate, he received the Alpheus Henry Snow Prize, awarded to the senior "who through the combination of intellectual achievement, character and personality, shall be adjudged by the faculty to have done the most for Yale by inspiring in classmates an admiration and love for the best traditions of high scholarship".

He studied at Oxford University as a Rhodes Scholar, earning a B.Litt.
in 1925.
At Harvard University, he quickly completed his M.A. in 1926 and Ph.D. degree in 1927.
He then returned to Yale to teach for two years, before beginning a distinguished teaching career at Harvard.
Matthiessen was born in Pasadena, California on February 19, 1902. He was the fourth of four children born to Frederick William Matthiessen (1868–1948) and Lucy Orne Pratt (1866). The family's three older siblings included Frederick William (1894), George Dwight (1897) and Lucy Orne (1898).
In Pasadena he was a student at Polytechnic School. Following the separation of his parents, he relocated with his mother to his paternal grandparents home in LaSalle, Illinois. His grandfather, Frederick William Matthiessen, was an industrial leader in zinc production and a successful manufacturer of clocks and machine tools. He also served as mayor of Lasalle for ten years. The grandson completed his secondary education at Hackley School, in Tarrytown, New York.
In 1923, Matthiessen graduated from Yale University, where he was managing editor of the Yale Daily News, editor of the Yale Literary Magazine and a member of Skull and Bones. As the recipient of the university's Deforest Prize, he titled his oration, "Servants of the Devil", in which he proclaimed Yale's administration to be an "autocracy, ruled by a Corporation out of touch with college life and allied with big business". In his final year as a Yale undergraduate, he received the Alpheus Henry Snow Prize, awarded to the senior "who through the combination of intellectual achievement, character and personality, shall be adjudged by the faculty to have done the most for Yale by inspiring in classmates an admiration and love for the best traditions of high scholarship".
He studied at Oxford University as a Rhodes Scholar, earning a B.Litt. in 1925. At Harvard University, he quickly completed his M.A. in 1926 and Ph.D. degree in 1927. He then returned to Yale to teach for two years, before beginning a distinguished teaching career at Harvard.
F. O. Matthiessen