March was born on December 27, 1864 in Easton, Pennsylvania, to Francis Andrew March and Mildred (Conway) March. His father was a college professor, and is regarded as the principal founder of modern comparative linguistics in Anglo-Saxon. His mother descended from Thomas Stone, a signer of the Declaration of Independence, and was Moncure D. Conway’s sister.

Peyton March attended Lafayette College, where his father occupied the first chair of English language and comparative philology in the United States. While at Lafayette College, March was a member of the Rho chapter of Delta Kappa Epsilon. After graduating with honors in 1884, he was appointed to West Point and graduated in 1888, ranked 10th in a class of 44.

March married Josephine Cunningham (née Smith, 18 December 1862 – 18 November 1904), the widowed daughter of his battery commander, Lieutenant Colonel Lewis Smith, on July 4, 1891. She died in November 1904, while March was still observing the Imperial Japanese Army. Between 28 November 1917 and 8 June 1918, their daughters Mildred (1893–1967), Josephine (1895–1972) and Vivian (1899–1932) had all married army officers. Josephine had a twin brother, named Peyton Jr. who died ten days after their birth. March’s second son, also named Peyton, Jr., was killed in a plane crash in Texas during World War I. March AFB in Riverside, California was named in his honor. A third son, Lewis Alden March, was born in 1904 and died in 1928.

After his initial assignment to the 3rd Artillery, March was assigned to the 5th Artillery as a 1st lieutenant in 1894. He was sent to the Artillery School at Fort Monroe, Virginia in September 1896 and graduated in April 1898, at the outbreak of the Spanish–American War. As he was not immediately assigned, he watched as his classmates went off to various commands, and began fearing he would not see combat. In early May, that changed when he was offered to lead what later became known as the Astor Battery, named so because it was personally financed by John Jacob Astor IV. He organized, equipped and subsequently commanded the battery when it was sent to the Philippines during the Spanish–American War. Historian Bruce Campbell Adamson has written about Henry Bidwell Ely (Adamson’s great grandfather) who was placed in charge of The Astor Battery by John Jacob Astor IV, to give Peyton March whatever he needed. March credited Ely as having “an open check book” to purchase uniforms, mules and the cannons.

After the battery returned from the Philippines in 1899, March was assigned as the aide to Major General Arthur MacArthur, Jr. during the Philippine–American War. Later that year he was promoted to major. He continued to serve in the Philippines, participated as part of General Loyd Wheaton’s expedition in battles at San Fabian, Buntayan Bridge and San Jacinto. He commanded the U.S. forces in the Battle of Tirad Pass, 2 December 1899, where General Gregorio del Pilar was killed, and received the surrender of General Venacio Concepción, Chief of Staff to Philippine President Aguinaldo at Cayan, 5 December 1899. He served as provincial governor of districts including Lepanto-Bontoc and Ilocos Sur from February to June 1900, and then the Abra Province from June 1900 to February 1901. He then served as Commissary General of Prisoners for the Philippine Islands through 30 June 1901, when he mustered out of the U.S. Volunteers.

In 1903, he was sent to Fort Riley and commanded the 19th Battery of the Field Artillery. Later that year, he was sent to Washington, D.C. and served on the newly created General Staff.

In 1907, March commanded the 1st Battalion, 6th Field Artillery. March then served as adjutant of Fort Riley, Kansas and then served as adjutant at several other commands, including at the War Department.

In 1916, he was promoted to colonel and commanded the 8th Field Artillery Regiment on the Mexican border during the Pancho Villa Expedition.

In June 1917, March was promoted to brigadier general and commanded the 1st Field Artillery Brigade, 1st Division, American Expeditionary Forces. Later that year, he was promoted to major general and commanded the artillery units of the First United States Army and all non-divisional artillery units.

In March 1918, he was recalled to Washington, took over as acting Army Chief of Staff on March 4 and was Army Chief of Staff on May 20, 1918. He was promoted to temporary general.

March was highly critical of President Wilson’s decision to send an American Expedition to North Russia and Siberia in 1918 during the Russian Civil War (the so-called Siberian Intervention) ostensibly to prop-up the White movement war effort, secure the railroads, support the Czech Legion trapped there, and stop the Japanese from exploiting the chaos in order to colonize Siberia. March wrote after the pull-out of American forces in 1920:

In 1919, March was admitted as an honorary member of the Virginia Society of the Cincinnati.

March retired as a major general in 1921 at the age of 56. In June 1930, March was advanced to general on the retired list as the result of a law which enabled World War I generals to retire at the highest rank they had held.

In December 1922, March was elected honorary president of Delta Kappa Epsilon during the fraternity’s 78th Annual Convention.

While traveling in Italy, he met Cora Virginia McEntee (1897–1964), and married her in August 1923.

After retirement, he travelled Europe, Africa and Turkey. In 1932, he published his war memoirs, The Nation at War. During World War II, reporters for Time and Life magazines regularly sought his opinions of events. He was a fan of the Washington Senators and regularly attended their home games.

March died at the Walter Reed Army Medical Center on April 13, 1955, and was buried at Arlington National Cemetery.