The third child of David McKay and Jennette Eveline Evans McKay, David Oman McKay was born on his father’s farm in Huntsville, Utah Territory, about 10 miles (16 km) east of Ogden. His mother, Jennette, was a Welsh immigrant from Merthyr Tydfil in south Wales. McKay’s father was a Scottish immigrant and was called on a two-year church mission to Scotland in 1880 after David O. McKay’s two older sisters died. The young David McKay took on responsibilities to help his mother.

McKay graduated from the University of Utah in 1897 as valedictorian and class president. Immediately afterward he was called on a mission to Great Britain. Like his father, he presided over the Scottish district of the church.

Upon his return in fall 1899, McKay taught at the high school level at LDS Weber Stake Academy (the predecessor of Weber State University) and became principal in 1902. He married Emma Ray Riggs in the Salt Lake Temple on January 2, 1901.

For his first three years at Weber McKay taught mainly religion and literature classes. On April 17, 1902 McKay was appointed principal of Weber succeeding Louis F. Moench, the founding principal who had resigned after nine years at the helm of the institution. One of his first actions as principal was the organize a school paper.

McKay also oversaw the inauguration of sports programs at Weber. In 1905 they won their baseball game against the University of Utah. There were also men's and women's basketball teams organized during McKay's tenure.

In 1905, Apostles John W. Taylor and Matthias F. Cowley resigned from the Quorum of the Twelve Apostles due to disagreement over the manifesto forbidding polygamy. In early 1906, Apostle Marriner W. Merrill died. With three vacancies in the quorum, George F. Richards, Orson F. Whitney and David O. McKay were called in the April General Conference of 1906. David O. McKay was only 32 at the time.

Prior to this calling to a full time church position, McKay had planned on a career in education and educational administration. Even after his calling, McKay stayed active in education. He continued serving as principal of the Weber Stake Academy until 1908 when he was replaced by Wilford M. McKendrick. He stayed on to see new building projects that he had inaugurated completed. He also served on the Weber school's board of trustees until 1922 and on the University of Utah's board of regents from 1921 to 1922.

McKay enjoyed a long personal friendship with John F. Fitzpatrick, publisher of The Salt Lake Tribune (1924–1960). They would meet once a week for breakfast to discuss the betterment of the state of Utah. Fitzpatrick, the architect of the Newspaper Agency Corporation, a joint operating agreement between The Salt Lake Tribune (Kearns Corporation) and the LDS owned Deseret News consulted extensively with McKay to form this mutually beneficial business in 1952.

In October 1906, McKay became an assistant to the superintendent of the Deseret Sunday School Union. At the time Joseph F. Smith was both president of the Church and Superintendent of the Sunday School, so much of the actual running of the organization was performed by McKay. After Smith died McKay became the Sunday School superintendent.

In 1920, the First Presidency assigned McKay to make a worldwide tour of the missions of the church with Hugh J. Cannon. They dedicated China for the preaching of the gospel, traveled to Hawaii where McKay first had the vision that led to the founding of BYU–Hawaii many years later, and traveled to Samoa, Tonga, New Zealand and Palestine. In Palestine they met up with Wilford Booth and visited the Armenian Latter-day Saints. They made it back to Utah on Christmas Eve, 1921.