With the outbreak of the American Civil War in 1861, Le Gendre helped recruit the 51st New York Volunteer Infantry; he was commissioned a major of that regiment on October 29, 1861.

At the Battle of the Wilderness in Virginia on May 6, 1864, while serving under General Ulysses S. Grant, Le Gendre was again severely injured, this time shot in the face with the bullet taking off his nose and left eye.

On July 13, 1866, Le Gendre was appointed to be American consul at Xiamen (then known by its Hokkien pronunciation "Amoy") in the Fujian Province of the Qing Empire.

As consul, Le Gendre was in control of five of the Treaty Ports open to foreign commerce in China: Xiamen, Keelung, Taiwan (modern-day Tainan), Tamsui, and Kaohsiung (then known as "Takao").

Le Gendre commissioned the United States steamer Ashuelot in order to visit the scene of the wreck and to try to get officials in Taiwan to act.

Both this and the subsequent American punitive expedition under Rear Adm. Henry Bell were failures; Le Gendre then returned to Taiwan without any reference to his superiors to gather more information.

Upon return to south China, Le Gendre managed to persuade the governor general in Fuzhou to send a military force to southern Taiwan.

Le Gendre quickly assumed de facto command of the mission, which entailed a long and difficult march deep into the mountainous interior of southern Taiwan.

Le Gendre negotiated an oral agreement guaranteeing the safety of shipwrecked American and European sailors with the chief of the aboriginal tribes in the area.

[4][5] However, Le Gendre was unexpectedly imprisoned for a brief time at Shanghai on the orders of the United States Consul-General for deserting the service, and thus never actually made it to Taiwan.

Among these are his four-volume Notes of Travel in Formosa (1874–1875), an intelligence report illustrated with photographs and paintings and published only in 2012 by the National Museum of Taiwan History.