Mulholland emigrates to Philadelphia with his parents while a boy. His youthful tastes incline him to military affairs and he becomes active in the ranks of the militia. At the outbreak of the Civil War he is commissioned lieutenant colonel of the 116th Pennsylvania Infantry, which is attached to Thomas Francis Meagher‘s Irish Brigade. When the regiment‘s size is reduced to a battalion, he accepts a reduction in rank to major.
Mulholland is wounded during the famous charge of the Irish Brigade up Marye’s Heights at the Battle of Fredericksburg on December 13, 1862. At the Battle of Chancellorsville on May 3 and 4, 1863, he leads his regiment and distinguishes himself by saving the guns of the 5th Maine Battery that had been abandoned to the enemy. For this he is complimented in general orders and later receives the Medal of Honor from the United States Congress. In this campaign he is given the command of the picket line by Major General Winfield Scott Hancock and covers the retreat of the Army of the Potomac across the Rappahannock River.
Although Mulholland later claims that at the Battle of Gettysburg on July 2, 1863 he personally took command of the 140th Pennsylvania Infantry and led it into action, this fact is mentioned in neither his own official report of the battle, nor that of the lieutenant colonel commanding the 140th. When the 116th is returned to full strength in early 1864, he is promoted to colonel. He is wounded a second time at the Battle of the Wilderness on May 5, 1864. At the Battle of Spotsylvania Court House he is wounded a third time, but remains in the hospital only ten days. Resuming his command, he is dangerously wounded again at the Battle of Totopotomoy Creek. He recovers rapidly and commands his brigade in all the actions around the Siege of Petersburg, particularly distinguishing himself by storming a fort on the Boydton Plank Road. He is mustered out of the volunteer service on June 3, 1865.
On May 4, 1866, President Andrew Johnson nominates Mulholland for the brevet grade of brigadier general of volunteers to rank from March 13, 1865 for his conduct at the Battle of the Wilderness and the U.S. Senate confirms the appointment on May 18, 1866. On January 13, 1869, President Johnson nominates Mulholland for appointment to the brevet grade of major general of volunteers, to rank from March 13, 1865 for his actions on the Boydton Plank Road and the Senate confirms the appointment on February 16, 1869. The brevet is issued February 20, 1869. It is the last brevet of major general issued for service during the Civil War.
Returning to civilian life after the war, Mulholland is appointed Chief of Police in Philadelphia in 1868, and signalizes his administration by the good order in which he keeps both the force and the city. President Grover Cleveland appoints him United States Pension Agent, in which office he is continued by Presidents William McKinley and Theodore Roosevelt. He is considered an authority on the science of penology, and also devotes much of his leisure time to art studies, and as a lecturer and writer on the Civil War and its records. He compiles a history of the 116th Regiment, and another of those to whom Congress voted the Medal of Honor. In the Catholic affairs of Philadelphia, he is always active and a leader among the best known laymen.
St. Clair Augustin Mulholland dies on February 17, 1910 in Philadelphia, Pennsylvania. He is buried at Old Cathedral Cemetery, Philadelphia.