Following further yard work and fitting out, Scorpion conducted shakedown operations off the southern New England coast in January 1943 and sailed for Panama in late February.

On an unrecorded date while she was on the surface at about the midpoint of her voyage from the Panama Canal Zone to Pearl Harbor, she encountered an Allied merchant ship which mistook her for a Japanese submarine and opened gunfire on her despite her efforts to identify herself.

There she underwent modifications which included the installation of a bathythermograph, a then-new oceanographic instrument to enable her to locate and hide in thermal layers that minimized the effectiveness of sonar equipment.

On 5 April, Scorpion departed Pearl Harbor for her first war patrol, a hunting and mining mission off the east coast of Honshū.

On 21 April, prior to 01:00, she fired on and destroyed her first sampan in surface action, then moved up the coast to observe the fishing grounds, shipping lanes, and coastline of the Shioya Saki area.

With the absence of shipping along the coastal lanes, she moved seaward and on 27 April sighted a convoy of four freighters escorted by a destroyer.

En route on 29 April, she sighted and engaged a 100 long tons (102 t) patrol vessel, which she left burning to the waterline.

On the morning of 30 April she stalked, fired on, and finally torpedoed and sank a 600 long tons (610 t) patrol ship Ebisu Maru No.5.

Scorpion submerged, survived the plane's depth charges and continued toward Midway Atoll and Pearl Harbor, arriving on 8 May.

Because of damage received during the depth charging, Scorpion retraced her route through Tokara Gunto; underwent a bomber attack east of Akuseki Jima; and continued on to Midway.

Poor weather continued to plague the submarine's hunting until, on 13 November, she sighted a freighter and a tanker escorted by three warships.

Departing Pearl Harbor on 29 December, Scorpion stopped at Midway to top off with fuel, and left that place on 3 January 1944 to conduct her fourth war patrol.

On the morning of 5 January, Scorpion reported that one of her crew members sustained a fractured foot via dropping a crate of oranges on it during the restocking of inventories in high seas.

The presence of these mine lines and the "restricted area" bounding them was discovered from captured Japanese Notices to Mariners at a much later date.

In the meantime, several submarines had made patrols in this area, crossing and recrossing the mine lines without incident, and coming safely home.

It is probable that these mine lines were very thin, offering only about a 10% threat to submarines at maximum, and steadily decreasing in effectiveness with the passage of time.