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Murrow was born near Polecat Creek, near Greensboro, in Guilford County, North Carolina, the youngest son of Quaker abolitionists. He was a "mixture of English, Scotch, Irish and German" descent. His home was a log cabin without electricity or plumbing, on a farm bringing in only a few hundred dollars a year from corn and hay.

When Murrow was five, his family moved to the state of Washington, homesteading thirty miles from the Canadian border, in Blanchard, Washington, on Samish Bay.

He attended high school in nearby Edison, becoming president of the student body in his senior year and excelling on the debating team. He was on the Skagit County championship basketball team. By that time, the teenage Egbert was going by the nickname "Ed".

In 1926, he enrolled in Washington State College in Pullman, Washington, eventually majoring in speech. A member of the Kappa Sigma Fraternity, Murrow was also active in college politics and in 1929, while attending the annual convention of the National Student Federation of America, his speech urging college students to become more interested in national and world affairs led to his election as president of the federation. He then moved to New York.

He worked as assistant director of the Institute of International Education from 1932 to 1935. He married Janet Huntington Brewster on March 12, 1935. Their son, Charles Casey was born November 6, 1945, in West London.