He served in the Union Army during the American Civil War, in which he was wounded twice, and was noted for his criticized performance during the 1864 Bermuda Hundred Campaign.

[3] At the beginning of the American Civil War in 1861, Wistar chose to follow his home state and the Union cause.

[4] On June 28, Wistar was promoted to the rank of lieutenant colonel,[3] and on July 1 the 71st left for Fortress Monroe on the Virginia Peninsula.

[3] Following the death of Col. Edward D. Baker at Ball's Bluff, Wistar became the commander of the 71st Pennsylvania, and was promoted to colonel on November 11, 1861.

[2] On November 29 Wistar was promoted to brigadier general, and he was assigned to brigade command in the VII Corps beginning on May 16, 1863.

[6] On May 7, Wistar resumed leading a brigade and participated in the Bermuda Hundred Campaign, but 11 days later he was relieved of duty and replaced by Col. Griffen Stedman.

He also served as president of the Pennsylvania State Board of Charities, the American Philosophical Society, and the Academy of Natural Sciences in Philadelphia.

[11] His New York Times obituary noted that the endowment he established prior to his death generated an annual return of $30,000.