Mather was born and grew up in Chicago, Illinois and graduated from South Chicago High School in 1904.

After graduating from Denison in 1909, he returned to the University of Chicago, where he completed his Ph.D. degree in 1915.

After completing his graduate studies, he held faculty positions at Queen's University (1915–1918) and Denison University (1918–1924), before beginning a 30-year teaching career at Harvard University in 1924.

In addition to his teaching duties at Harvard, he served as the Director of the Harvard Summer School from 1933 through 1938.

In 1938, he served as the head of the Association of Summer Session Deans and Directors.

In 1951, he became a member of the board of trustees for Science Service, now known as Society for Science & the Public.

He served as board president of the American Association for the Advancement of Science from 1948-1956 and the American Academy of Arts and Sciences from 1957–1961.

For his scholarship in the field of geology, he was awarded the Cullum Geographical Medal in 1965.

Mather is known for his role in the 1925 Scopes "Monkey Trial".

By 1924 Mather had already perceived the threat of biblical literalism as used by some segments of the religious Right.

A harbinger of Mather’s willingness to stakeout unpopular positions in the service of academic freedom is what his biographer, Kennard Bork refers to as the “Kornhauser Affair” at Denison University in 1922.

Massachusetts Teachers’ Oath Mather took a leadership role in resisting the Massachusetts Teachers' Oath of 1935.

In 1937, Mather co-founded the Institute for Propaganda Analysis with Edward A. Filene and Clyde R. Miller.

A measure of the Red Scare price that Mather would pay for his activism is reflected in the April 4, 1949, issue of Life magazine.

Personal life Mather was married twice, first to Marie Porter Mather from 1912 until her death in 1971.

He married Muriel Williams Mather in 1977.

Upon his retirement from Harvard in 1954, he and Marie traveled widely around the world, finally settling in Albuquerque, New Mexico, where he resided until his death at the age of 90.

Mather died in 1978 in Albuquerque and is buried in Granville, Ohio.

In 1982, Lynn Elfner reflected on the Scopes Trial and Mather's legacy:

Published works 1922: Front Ranges of the Andes between Santa Cruz, Bolivia, and Embarcación, Argentina, Geological Society of America Bulletin,

Beneath Us, photos by Josef Muench, drawings by Howard Morris, Random House, ISBN 0394422910 (translated into French, German, Italian and Dutch; winner of the 1964 Thomas A. Edison Award and the 1964 Book Award of the Geographic Society of Chicago.