Ernest L. Wilkinson was born in Ogden, Utah, on May 4, 1899. He attended school at the Weber Academy and its successor Weber Junior College. He served as editor of the school paper and was president of the student body twice. He was also a member of the state championship debating team, valedictorian, and winner of an award given to the best all-around student.

On October 25, 1918 Wilkinson was inducted into the Brigham Young University Student Army Training Corps and served until the end of World War I. Upon discharge, he returned to Ogden and organized the Ogden Transportation Company. In 1919 he enrolled at Brigham Young University and graduated with a Bachelor of Arts degree in 1921. While at BYU, Wilkinson served as president of his class, won a University-wide extemporaneous speaking contest, was a member of several debating teams, edited the school newspaper, and founded the Public Service Bureau.

It was at BYU that Wilkinson met Alice Ludlow. They courted for a couple of years and were married in 1923. They became the parents of three sons and two daughters, all of whom attended Brigham Young University.

Following his graduation, Wilkinson taught English and public speaking at Weber College until 1923, when he entered the law school at George Washington University. He graduated summa cum laude with a Bachelor of Law Degree in 1926 and was awarded a scholarship to Harvard University Law School where he attained the degree of Doctor of Juridical Science in the spring of 1927. While at Harvard, he wrote two theses: Administrative Control of Irrigation and Irrigation Rights in Inter-state Streams. Upon graduation he was appointed assistant professor of law at the University of California, a position which he almost immediately resigned to become a professor of law at the New Jersey Law School. After a few months of teaching full-time, Wilkinson realized that he didn't want to teach for the rest of his life. He practiced law in New York as an associate of Hughes, Schurman and Dwight, the law firm established by future Supreme Court Justice Charles Evans Hughes. There he gained experience in trial work, anti-trust law and corporate reorganizations. He was also able to continue teaching at the New Jersey Law School in the evening.

In 1935 Ernest L. Wilkinson entered into partnership with Walter Gladstone Moyle in Washington, D. C. They practiced law together for five years before Wilkinson decided to organize his own law firm in 1940 and named it Wilkinson, Cragun, and Barker. While an associate at Hughes, Schurman and Dwight, Wilkinson began working on a case involving the Ute Indians. Because Hughes, Schurman and Dwight did not want to pursue the Ute Indian case, Wilkinson was allowed to take the case with him when he established his own law firm. Wilkinson continued work on the case until 1950 when the Utes were awarded several judgements totaling $31, 928, 473. During his involvement in this litigation, Wilkinson was instrumental in the establishment of the Indian Claims Commission which greatly benefitted Indian tribes in their claims against the United States government.

On July 15, 1950, Ernest L. Wilkinson was approached by the president of the Church of Jesus Christ of Latter-day Saints, George Albert Smith, about becoming President of Brigham Young University. He formally accepted the position on July 27, 1950 but did not begin work until the fall of 1951 because of commitments to his law firm. He served as President of Brigham Young University until August 31, 1971. His tenure as president was interrupted briefly in 1964 when Wilkinson was granted a leave of absence during which he unsuccessfully ran for the United States Senate.

During his twenty years at the helm, Brigham Young University experienced tremendous growth. Enrollment grew from around 4,000 students to nearly 25,000 students. The number of buildings on campus grew from twenty to more than one hundred. Academically, BYU went from five colleges to thirteen colleges and experienced a complete revision of the curriculum. Associate and doctoral degrees were added to the bachelor's and master's degrees already offered. The University changed from the quarter system to the semester system, scholarships were expanded, and the Honors Program was established. Under his leadership a number of new programs were instituted including the Army and Air Force ROTC, the weekly forum of great speakers, intramural sports, the Institute of Government Service, and the Institute of Mormon Studies. The total number of faculty increased from 193 to 1,070, with the proportion of faculty holding doctoral degrees increasing from 26% to 54%. The number of graduate degrees awarded annually increased over ten times, to 840. During this time period BYU's performing groups traveled all over the world and the university's athletic programs achieved national prominence in many areas. Perhaps, his proudest achievement was the establishment of wards and stakes of the Church of Jesus Christ of Latter-day Saints on campus. When he became university president one branch of the Church existed on campus; in 1971 ten stakes with ninety-eight wards were operating.

In addition to being president of Brigham Young University, Wilkinson was chancellor of the Unified Church School System from 1953 to 1964. The Unified Church School System consisted of BYU, a junior college, 161 institutes of religion near colleges and universities, 1,658 seminaries near high schools, the Brigham Young Laboratory School, LDS Business College, and two academies and twenty-four elementary schools in Mexico.

Following his resignation as president of Brigham Young University, Ernest L. Wilkinson directed the research and writing of a four-volume Centennial History of BYU and a one-volume summary history. He passed away following a heart attack in April 1978.