A native of Daloe, Norway, John Andreas Widtsoe immigrated to the United States with his mother and younger brother Osbourne after converting to Mormonism. They arrived in Logan, Utah in November 1883. In 1889, Widtsoe entered the Brigham Young College, under the tutelage of BYC President Joseph M. Tanner. Tanner later served as President of the UAC from 1894 to 1899. Tanner helped effectuate Widstoe's attendance at Harvard University, where he graduated in 1894. After graduation, Widtsoe returned to Logan to head Chemistry work for Agricultural Experiment Station. In 1898, he enrolled at the University of Goettingen, Germany, and was awarded a Ph.D in 1899. Also in 1898, Widtsoe married Leah Eudora Dunford, whom he had first met while in Cambridge, England five years earlier. In 1900, the couple returned to Logan, where Widtsoe became Director of the Experiment Station.

Following the resignation of his mentor Joseph M. Tanner from the UAC presidency, a minority of the college's Board of Trustees championed Widtsoe as his successor. The board divided over Widtsoe's candidacy, with the majority supporting William J. Kerr. Widstoe continued directing the Experiment Station through 1905, when a disagreement with Kerr resulted in his dismissal. For the next two years, Widtsoe directed his energy to establishing an agricultural program at Brigham Young University in Provo. In 1907, he returned to Logan as the newly elected President of the UAC.

Widtsoe assumed the presidency amidst controversy, as the Board of Trustees again divided on his candidacy. This time, however, the Board supported his candidacy, and rather elected to dismiss President Kerr. Widtsoe also began his tenure as president following a legislative mandate that had restricted the College's curriculum. After 1907, the College was mandated to concentrate on agriculture, mechanical arts and domestic science, and was prohibited from offering courses in engineering, law, medicine or pedagogy, a curriculum that the State Legislature viewed as more appropriately being offered at the University of Utah.

Widtsoe served as College President through 1915, when he was selected to become the President of the University of Utah in Salt Lake City.