He held Congregational pastorates at Amesbury, Massachusetts (1878–83), where in 1880 he married Mary Goodale Montgomery, and in Baltimore, Maryland (1883–88).

Along with his new wife, Mary Goodale Montgomery, Slocum ministered to the social and economic needs as well as the religious needs of his Amesbury parishioners.

While in Baltimore, Slocum received a visit from Professor George N. Marden of Colorado College, who was on a fund-raising trip on the East Coast.

Slocum strongly emphasized the religious side of education, giving Friday morning chapel sermons called "Ethicals."

[7] Later, when a major fire roared through Cripple Creek, Slocum mobilized the students of Colorado College to canvas nearby residential areas for clothing, food, and firewood to help the burned out gold miners and their families.

One of the teachers in the summer school was Katherine Lee Bates, a professor of English at Wellesley College in Massachusetts.

Bates was so inspired by the view of the mountains and the plains from atop Pike's Peak that she wrote a poem entitled "America The Beautiful."

In the ensuing celebration, the men students pulled Slocum around the campus and downtown Colorado Springs in a buggy.

An amused onlooker noted: "The center of interest was President Slocum, trying not to look too unhappy, seated in a high run-a-bout, drawn by students who were in cap and gown, and clasping to him a large money bag (made...of one of Mrs. Slocum's soft pillows) with $150,000 on it in large figures."

"[10] Slocum gained a national reputation as the successful leader of a western small liberal arts college.

He received honorary degrees from Amherst College (his alma mater), Harvard University, and five other institutions of higher learning.

"[13] Soon afterward, the Board of Trustees asked for the resignation of Edward Parsons, the dean who had brought forward the accusations.

Dunn, Joe P. (2010), "'Scandal on the Plains: William F. Slocum, Edward S. Parsons, and the Colorado College Controversies'", Great Plains Quarterly; Fauvel, John, 'Monicagate on Cache La Poudre Street: The end of the golden age at Colorado College' William and Mary Slocum moved to the Boston-area town of Newton, Massachusetts.

In 2018, in light of renewed attention to Slocum's sexual misconduct on the centennial of his departure, Colorado College removed his name from two buildings, took down his portrait, and rescinded an honorary doctorate that it had given him at his resignation.

[14] One of Slocum's greatest contributions to Colorado College was the construction of ten major academic and residential buildings.