Cyrus Walker was born at the Whitman mission of Waiilatpu in 1838. He was the first baby boy born to two white parents in the Pacific Northwest.
His mother and father, Mary Richardson and Elkanah Walker, were Congregationalist missionaries. For the first ten years of his life, Cyrus lived at his family's mission to the Spokane at Tshimakain, northwest of the modern city of Spokane, Washington. He grew up speaking English and Spokane. When the Whitmans were killed in a dispute with the Cayuse in 1848, the Walkers evacuated to Oregon City. They moved again the next year to a fledgling community in the West Tualatin Plains of Oregon. The small village where they took a claim would later be called Forest Grove. Cyrus' parents helped found Tualatin Academy (a high school) and Pacific University, donating some of the land for the campus. In 1859, Cyrus would become one of Tualatin Academy's first graduates.