From commissioning until December 1938, she served as the flagship of the Yangtze River Patrol, operating out of Hankou, between such ports as Nanjing, Chongqing, and Shanghai.

Luzon arrived at Manila on 30 December, just 23 days after the Japanese attack on Pearl Harbor brought the United States into World War II.

She then began patrol operations in the waters of the Philippines, assisting in the defense of both Bataan, from 1 February until the surrender of the peninsula to the Japanese 9 April, and Corregidor, from the beginning evacuations of that entrance island to Manila Bay until the enemy landings 5 May.

Although classified by the Japanese as a riverine gunboat, repair work continued to convert her into a sea-going submarine chaser, including the installation of a sonar system.

Unable to complete the work in time, the IJN decided to scuttle her in order to block a channel in Manila Bay on 5 February.