7 December 1941, Mutsuki was the flagship of Destroyer Division 30 under Destroyer Squadron 6 of the 4th Fleet. She sortied from Kwajalein on 8 December as part of the Wake Island invasion force, carrying an advance landing party of the Japanese Special Naval Landing Forces (SNLF). Early on the morning of 11 December, the American garrison repulsed the first landing attempts by the SNLF, which was supported by the light cruisers , , and and the destroyers , , , Mutsuki, , and , two old vessels converted to patrol boats (Patrol Boat No. 32 and Patrol Boat No. 33), and two troop transports containing 450 SNLF troops. After taking heavy losses (including Kisaragi and Hayate), the Japanese force withdrew before landing. This was the first Japanese defeat of the war, and also the only occasion in World War II when an amphibious assault was repulsed by shore-based guns. Mutsuki returned on 23 December with the second Wake Island invasion force, and again carried a SNLF advance landing party before returning to Kwajalein. The ship escorted a convoy from Kwajalein to the naval base at Truk in January 1942, where a sponson was installed for a pair of license-built Type 93 anti-aircraft machineguns on the forward side of the bridge. Mutsuki then escorted a troop convoy from Truk to Guam later that month, and then joined the invasion of the Solomon Islands, covering the landings of Japanese forces during Operation R (the invasion of Rabaul, New Ireland and New Britain), and during Operation SR (the invasion of Lae and Salamaua on New Guinea) in January–March. From 28 March to 1 April, she served as the flagship for Rear Admiral Masao Kanazawa, commander of the 8th Special Base Force during the initial occupation of the Shortland Islands and Bougainville in the Solomon Islands. Later that month, the ship supported the occupation of the Admiralty Islands. During the Battle of the Coral Sea from 7–8 May 1942, Mutsuki was assigned to the Operation Mo invasion force for Port Moresby. After that operation was cancelled, Mutsuki remained based out of Rabaul, escorting shipping between Truk, Rabaul and Palau until recalled to Japan in July for a brief refit. After repairs were completed at Sasebo Naval Arsenal on 12 July 1942, Mutsuki was reassigned to the IJN 8th Fleet and participated in the bombardment of Henderson Field on 24 August 1942. During the