His grandfather, Joshua, was the "Father of the American Navy", who had served as chief naval constructor from 1794 to 1801 and designed the first U.S. warships, six frigates, the USS Constitution ("Old Ironsides") and her sister ships.

Near the beginning of the Seminole Wars he followed his regiment in the summer of 1836 to Florida where he received his first combat experience, while also falling ill, having to leave by September.

Of the next twenty-three years each one was illustrated by some distinguished engineering achievement which won for him a reputation at home only exceeded by that what he acquired abroad.

[3] After being reinstated in the engineer corps in 1844 Humphreys was put in charge of the Central Office of the Coast Survey at Washington and appointed to captain in 1848.

During 1850 he was directed to commence surveys and investigate the Mississippi River Delta in order to figure out what could prevent inundation and increase the depth of water on the bars.

[5] After the outbreak of the Civil War, Humphreys was promoted on August 6, 1861, to major and became chief topographical engineer in Maj. Gen. George B. McClellan's Army of the Potomac.

Humphreys was promoted to brigadier general of volunteers on April 28[8] and on September 12 assumed command of the new 3rd Division in the V Corps of the Army of the Potomac, two brigades of nine month regiments mustered in in August.

At the Battle of Fredericksburg, his division achieved the farthest advance against fierce Confederate fire from Marye's Heights, with Humphreys personally commanding from the very front of the line on horseback, while five of his seven staff were shot down.

Gen. Daniel Butterfield, wrote: "I hardly know how to express my appreciation of the soldierly qualities, the gallantry, and energy displayed by my division commanders, Generals George Sykes, Humphreys, and Charles Griffin.

Historian Larry Tagg wrote: ... for certain good reasons connected with the effect of what I did upon the spirit of the men and from an invincible repugnance to ride anywhere else, I always rode at the head of my troops."

After his men had taken as much as they could stand in front of the Stone Wall on Marye's Heights, the next brigade coming up the hill saw Humphreys sitting his horse all alone, looking out across the plain, bullets cutting the air all around him.

His new division immediately saw action at Gettysburg where, on July 2, 1863, Sickles insubordinately moved his corps from its assigned defensive position on Cemetery Ridge.

Humphreys' new position was on the Emmitsburg Road, part of a salient directly in the path of the Confederate assault, and it was too long a front for a single division to defend.

Humphreys was promoted to major general of volunteers on July 8, 1863,[12] and finally acceded to Meade's request to serve as his chief of staff;[13] as his division was decimated in the fighting at Gettysburg.

In November 1864, he assumed command of the II Corps after Winfield Hancock was forced to resign for health reasons, which he led for the rest of the siege and during the pursuit of Gen. Robert E. Lee to Appomattox Court House and surrender.

Humphreys's published works were highlighted by the 1861 Report on the Physics and Hydraulics of the Mississippi River,[16] co-authored with Lt. Henry Abbot,[1] which gave him considerable prominence in the scientific community.