On 7 December 1941, "I-121" laid forty-two Type 88 Mark 1 mines northeast of Singapore in the vicinity of . She then took up her patrol station off the eastern entrance of Johore Strait. In East Asia, World War II began on 8 December 1941, and Japanese forces invaded British Malaya to the north of Singapore that day. Reassigned to the Southern Submarine Force, she called at Cam Ranh Bay in Japanese-occupied French Indochina on 12 December 1941, then got back underway the same day to support the Japanese invasion of the Philippines, bound for the vicinity of Davao on Mindanao. She supported the Japanese landings at Davao on 19–20 December 1941 and at Jolo on 24 December 1941. Reassigned to Submarine Group "A" along with "I-122", "I-123", and "I-124" on 26 December 1941, she concluded her patrol on 27 December 1941 with her arrival at newly captured Davao.