At the outbreak of the Civil War in 1861, von Vegesack left for the United States and joined the Union Army. He became captain of the 58th Ohio Infantry. The same year, he was promoted to major in the staff of general John E. Wool. First he served in Fort Monroe. As an aide-de-camp (ADC) to Joseph K. Mansfield he took part in the artillery bombardment of Newport News. In 1862 he resigned, but then he joined Major General George B. McClellan in his siege of Yorktown. As an ADC to Butterfield he took part in the battles of Hanover Court House, of Seven Pines and of Fair Oaks. He was at the Battle of Mechanicsville, Gaines's Mill, Savage's Station, and Malvern Hill. Vegesack was appointed colonel of the 20th New York Infantry, the German "Turner" regiment. He was given the command over the 3rd brigade in General William Farrar Smith's division of the 6th Army Corps. He took part in the Second Battle of Bull Run. He captured the heights outside Jefferson, Maryland. He displayed bravery at Antietam. Vegesack was in the Battle of Fredericksburg. In May 1863 Vegesack's regiment was a part of Joseph Hooker's left wing in the Battle of Chancellorsville.