Born at Oakland, one of the Nelson family plantations, in the village of Beaverdam in Hanover County, Virginia to John Page and Elizabeth Burwell Nelson. He was a scion of the prominent Nelson and Page families, each First Families of Virginia. Although he was from once-wealthy lineage, after the American Civil War, which began when he was only 8 years old, his parents and their relatives were largely impoverished during Reconstruction and his teenage years. In 1869, He entered Washington College, known now as Washington and Lee University, in Lexington, Virginia when Robert E. Lee was president of the college. After three years, Page left Washington College before graduation for financial reasons. To earn money for the law degree he desired, Page taught the children of his cousins in Kentucky. From 1873 to 1874, he was enrolled in the law school of the University of Virginia in pursuit of a legal career.

Admitted to the Virginia Bar Association, he practiced as a lawyer in Richmond between 1876 and 1893, and began writing. He was married to Anne Seddon Bruce on July 28, 1886. She died on December 21, 1888 of a throat hemorrhage.

He remarried on June 6, 1893, to Florence Lathrop Field, a widowed sister-in-law of retailer Marshall Field. In the same year Page gave up his law practice entirely and moved with his wife to Washington, D.C..There, he kept up his writing, which amounted to eighteen volumes when they were compiled and published in 1912. Page popularized the plantation tradition genre of Southern writing, which told of an idealized version of life before the Civil War, with contented slaves working for beloved masters and their families. His 1887 collection of short stories, In Ole Virginia, is the quintessential work of that genre. Another short-story collection of his is entitled The Burial of the Guns (1894).

Under President Woodrow Wilson, Page served as U.S. ambassador to Italy for six years between 1913 and 1919. His book entitled Italy and the World War (1920) is a memoir of his service there.

He died in 1922 at Oakland in Hanover County, Virginia.

Page was an activist in stimulating the Association for the Preservation of Virginia Antiquities to mobilize to save historical sites at Yorktown and elsewhere, especially in the Historic Triangle of Virginia, from loss to development. He was involved in gaining Federal funding to build a seawall at Jamestown in 1900, protecting a site where the remains of James Fort were later discovered by archaeologists working on the Jamestown Rediscovery project which began in 1994.

The Page and Nelson families were each among the First Families of Virginia. The Page lineage in Virginia began with the arrival at Jamestown of Colonel John Page at Jamestown in 1650. Col. Page was a prominent founder of Middle Plantation, which was later renamed Williamsburg. The Page family included Mann Page, U.S. Congressman and Governor John Page. The Nelson lineage began with Thomas "Scotch Tom" Nelson, a Scottish immigrant who settled at Yorktown, and his son, William Nelson, who was a royal governor of Virginia. Thomas Nelson Page was a direct descendant of Thomas Nelson, Jr., a signer of the Declaration of Independence and a governor after Statehood, and thus of Robert "King" Carter, who served as an acting royal governor of Virginia and was one of its wealthiest landowners in the late 17th and early 18th centuries. The Nelson family had settled in Hanover County, where Thomas's mother Elizabeth Burwell Nelson, married John Page.

A contemporary cousin of Thomas Nelson Page was William Nelson Page (1854-1932), who became a civil engineer and mining manager had helped develop the natural resources of western Virginia and southern West Virginia in the late 19th and early 20th centuries. William Page is credited with, in partnership with millionaire financier Henry Huttleston Rogers, planning and Building the Virginian Railway. His family's Victorian-era mansion, the Page-Vawter House in Ansted, West Virginia, is a National Historical Landmark as is a former company store of the Page Coal and Coke Company in Pageton.Other cousins were Confederate officers Robert Edward Lee and Richard Lucian Page

The ruins of Rosewell Plantation, the home of early members of the Page family and one of the finest mansions built in the colonies, sit on the banks of the York River in Gloucester County. In 1916, a fire swept the mansion leaving a magnificent shell which is testament to 18th century craftsmanship and dreams. There are ongoing archaeological studies at the site.