While she steamed toward the New Hebrides Islands via the Panama Canal and Pearl Harbor, the Navy daringly launched its first offensive thrust against Japan by landing the 1st Marine Division on Guadalcanal and Tulagi.

While awaiting the arrival of the PT boats of Squadron 3, the tender busied herself escorting resupply convoys between the New Hebrides and Tulagi towing a barge carrying 2,000 barrels (320 m3) of gasoline and 500 quarter-ton bombs.

Cargo ship Bellatrix assisted her in towing them to Espiritu Santo, where Jamestown entrusted them to two fast minesweepers for the final passage to Tulagi and resumed her efforts to keep vital supplies flowing through the enemy infested waters to the Marines on Guadalcanal.

For the next 4 months these fearless little ships patrolled "Iron Bottom Sound" nightly, frequently challenging Japanese destroyers, cruisers, and even battleships of "the Tokyo Express".

Besides ministering to the PT boats, the tender assisted with preliminary repairs to battle-damaged American cruisers and sent parties ashore to construct pipelines to water holes.

Jamestown and the PT boats of Squadron 3 were explicitly included in the Presidential Unit Citation awarded the 1st Marine Division for taking and holding strongly defended Japanese positions on Tulagi, Gavutu, Tanambogo, Florida Island, and Guadalcanal.

She departed Tulagi 18 February 1943 on one of countless trips made during the following year from that port to the New Hebrides or Rendova for supplies for the PT boats or acting as escort between island groups.