At the time of the attack on Pearl Harbor, "Uzuki" was part of Desron 23 under Carrier Division 2 in the IJN 1st Air Fleet, and deployed from Hahajima in the Ogasawara Islands as part of the Japanese invasion force for the Invasion of Guam. She returned to Truk in early January 1942 to covering the landings of Japanese forces during "Operation R" at Kavieng, New Ireland on 23 January, returning to Truk one month later. In March, "Uzuki" assisted in covering landings of Japanese forces during "Operation SR" in the northern Solomon Islands, Lae and Admiralty Islands. The destroyer was reassigned to the IJN 4th Fleet on 10 April. During the Battle of the Coral Sea from 7–8 May 1942, "Uzuki" was assigned to escort the tanker "Hoyo Maru" in the Shortlands area, and returned to Sasebo Naval Arsenal for refitting on 28 May. By the end of June, "Uzuki" was based at Truk, and assigned to escort convoys carrying airfield construction crews from Truk to Bougainville and Guadalcanal, and patrols around Rabaul. During the invasion of Buka (21–22 July), "Uzuki" was strafed by Allied aircraft, with loss of 16 crewmen. On 11 August, "Uzuki" sortied from Rabaul to rescue the survivors of the cruiser . At the end of August, while on a "Tokyo Express" transport run to Guadalcanal, "Uzuki" suffered damage from a near miss in an attack by USAAF B-17 Flying Fortress bombers, and returned via Rabaul, Truk and Saipan back to Sasebo for repairs on 14 September.