[citation needed] His mother Catherine died shortly after Edward's birth, and afterwards his father married Martha Anne Fontaine Pope.

[citation needed] He was the grandson of Congregationalist minister Heman Humphrey, an author of theological treatises and the second president of Amherst College.

[5][6][7] During his long career on the Board of Trustees of Centre College, he was in charge of the school's extensive property interests.

[8] In 1874 Humphrey was appointed as director and treasurer of the Louisville Law Library Company, a position for which he was re-elected for forty-four successive terms.

Humphrey and Thomas Speed, a United States representative from Kentucky were designated to notify the Presbytery of the members' vote to accept the resignation of the church minister.

In 1901, an overflow crowd gathered to hear discussions on Presbyterian creed revision which was held at Princeton Theological Seminary.

"[9][14] On the final vote of the Presbyterian General Assembly, all of the committee's creed changes were accepted except those not recommended by Humphrey and McKibben, who led the dissenting opinion on those changes.