Leftwich sailed from Pascagoula, MS the morning following the commissioning on 26 August 1979, en route via the Panama Canal for her homeport, Naval Station San Diego, from which she operated until March 1985.

On sailing, Hurricane David was threatening to make its way into the Gulf of Mexico, so shipping traffic on the transit to the Panama Canal was unusually light.

In January 1980, Leftwich returned to Litton Industries at Pascagoula, MS for Warranty repairs and a Post-Shakedown Availability, which included the installation of the NATO Sea Sparrow and Harpoon missile system.

On 29 November 1982 she collided with the submarine USS Thomas A. Edison (SSBN-610) approximately 40 miles (64 km) east of Subic Bay, Philippines.

Two months later, Thomas A. Edison made a surface transit to Puget Sound Naval Shipyard for decommissioning without the damage having been repaired.

In 1984, Leftwich suffered hull and sonar window damage due to high-speed operations in heavy seas during fleet exercises on her deployment to Indian Ocean/Western Pacific (WESTPAC 1984).

This was a response to Iran's 16 October 1987 attack on the MV Sea Isle City, a reflagged Kuwaiti oil tanker at anchor off Kuwait, with a Silkworm missile.