Alexander Swift Pendleton was born near Alexandria, Virginia, on September 28, 1840, the son of William Nelson Pendleton and Anzolette E. Page. In 1853 his father, an 1830 graduate of the United States Military Academy at West Point, was appointed an Episcopal minister in the Shenandoah Valley town of Lexington. The younger Pendleton entered Lexington's Washington College that fall and was graduated in 1857 having won the college's highest academic award. Two years later he entered the University of Virginia to pursue a master's degree. His graduate studies and plans to enter the ministry were cut short, however, when Virginia seceded in April 1861.

Pendleton served unofficially with his father's command, the Rockbridge Artillery—a unit formed by John A. McCausland and a part of the Stonewall Brigade. In June, Jackson asked him to join his staff as a second lieutenant and brigade ordnance officer. Appointed a first lieutenant in November, Pendleton became Jackson's de facto chief of staff during the Shenandoah Valley Campaign of 1862, in spite of Robert Lewis Dabney's grade of major and official designation as Jackson's assistant adjutant general.

Pendleton was an inspired choice. He was equally comfortable in battle relaying orders or encouraging troops, on the march coordinating officers and units, or in camp handling the endless correspondence and other paperwork required to make the army run. Jackson prized Pendleton's intelligence, attention to detail, and boundless energy. When asked for frank assessments of several lower-ranking officers, Jackson replied, "Ask Sandie Pendleton. If he does not know, no one does." A. Cash Koeniger has observed that Pendleton was one of only a few officers, most of them "notable for their pronounced faith in God" as well as for their devotion to duty, who got along well with the notoriously irascible and judgmental general. Jackson recommended Pendleton for promotion to captain just after the end of the Valley Campaign.

Pendleton, with Jackson at the Seven Days' Battles during the summer of 1862, missed the Second Manassas Campaign in August on sick leave, but returned to duty in time for Robert E. Lee's first invasion of the North and the Battle of Antietam on September 17. After being slightly wounded at Fredericksburg in December, Pendleton was promoted to major and assistant adjutant general in the Army of Northern Virginia's new Second Corps, commanded by Jackson. He was already among the most respected staff officers in Lee's army.

Pendleton was on another part of the battlefield, however, and not with Jackson's party on the night of May 2, 1863, when it was accidentally fired on by Confederate pickets at Chancellorsville. Jackson was wounded and died a few days later following the amputation of his left arm. "God knows," Pendleton later told Jackson's wife Mary Anna, "I would have died for him."

He tendered his resignation, believing that Jackson's successor Richard S. Ewell should choose his own staff, but Ewell retained him, recommending him for promotion to lieutenant colonel and chief of staff in August 1863. When Lee replaced Ewell with Jubal A. Early in May 1864, Pendleton kept the same position. He accompanied Early during the Shenandoah Valley Campaign of 1864 with a new Army of the Valley, created with the Second Corps as its nucleus.

On September 22, 1864, Early's Confederates were overwhelmed and utterly routed at Fisher's Hill, their second defeat in four days. Pendleton, trying to rally men streaming to the rear, was mortally wounded. He died the next day, less than a week before his twenty-fourth birthday. He is buried in Lexington, not far from the grave of Stonewall Jackson.