Sent to the Pacific Ocean to search for the CSS Alabama, Wyoming eventually came upon the shores of Japan and engaged Japanese land and sea forces.

She was instructed to remain in the vicinity of the Golden Gate to protect mail steamers operating off the California coast, but CDR Mitchell — a naval officer of Southern origin and persuasion — defied his orders and took his ship to Panama instead.

First, her bottom struck a coral head off La Paz, Baja California Sur, and was pulled free only after three days aground during which she lost her false keel.

Following repairs at Mare Island, Wyoming received orders — dated 16 June 1862 — to proceed immediately to the Far East in search of "armed piratical cruisers fitted out by the rebels" and soon headed west, bound for the Orient.

In the Sunda Strait, off Java, Captain Raphael Semmes, the commanding officer of Confederate cruiser Alabama, learned from an English brig of Wyoming's arrival in the East Indies; and a Dutch trader later confirmed this report.

Yet, despite being unsuccessful in tracking down Confederate cruisers, Wyoming did render important service to uphold the honor of the American flag in the Far East the following year, 1863.

Ordered to Philadelphia that spring — after what had been a largely fruitless cruise — Wyoming was in the midst of preparations to leave the East Indies when an event occurred that changed her plans.

Nevertheless, that agitation continued into the early summer months, as the sonnō jōi movement grew in strength with increasing resentment by the Japanese to the terms of the recent unequal treaties signed with the western powers.

At one o'clock on the morning of 26 June, two armed vessels of Chōshū Domain attacked the American merchantman Pembroke, bound for Nagasaki and Shanghai, as she lay anchored in the Strait of Shimonoseki.

Pembroke suffered no casualties; got underway; and moved out of danger, escaping via Bungo Strait and continuing her voyage for Shanghai, post-haste, without making her scheduled stop at Nagasaki.

Writing from Batavia on 22 November, McDougal later reported that Wyoming had scoured the waters of the East Indies, visiting "every place in this neighborhood where she (Alabama) would likely lay in case she intended to remain in this region."

Although acknowledging that the condition of Wyoming's boilers prevented a heavy pressure of steam from being carried, McDougal promised to make every effort in his power to find and capture Alabama.

When the sloop-of-war reached Batavia, however, CDR McDougal found that there was now no alternative but to return to the United States for repairs, because the ship's boilers were in such poor condition.

Commodore Cornelius Stribling, Commandant of the Philadelphia Navy Yard, ordered the newly arrived screw sloop to sea to search for Florida.

For five days, the ship attempted to carry out the orders given her — contending with fresh northeast winds and a head sea — but returned to Philadelphia on 19 July, due to a leaky boiler.

John P. Bankhead in command, Wyoming proceeded to the East Indies Station, via Cape Horn, and reached Singapore on 25 September 1865, in time to participate in the search for CSS Shenandoah, a Confederate raider which remained at sea for one month after the end of the Civil War.

On 13 June, she participated in a punitive expedition against Formosan natives who had murdered the crew of the American merchant bark Rover that had been wrecked off the coast of Formosa a short time before.

Subsequently, returning to the United States having performed her last service in the Far East, Wyoming was decommissioned on 10 February 1868 and placed "in ordinary" at Boston, Massachusetts.

; Aspinwall, Panama; Santiago, Cuba; Kingston, Jamaica; San Juan, Puerto Rico; Key West; Hampton Roads, Va.; and New Bedford, Mass.

After that tour of duty, cruising and "showing the flag" in the West Indies and Gulf of Mexico, Wyoming was decommissioned at the Washington Navy Yard on 30 April 1874 and remained laid up there for the next two years.

In 1876, the Wyoming was deployed to the Potomac river in order to defend Washington DC at rumors of an invasion by Southern separatists after the controversial election between Rutherford B. Hayes and Samuel J. Tilden.

Recommissioned on 20 November 1877, Wyoming left Washington, loaded articles for the Paris Exposition, and departed the East Coast of the United States on 6 April 1878, bound for France.

Wyoming remained in the Mediterranean into November 1880, touching at many of the more famous ports in that historic body of water — and in the Black Sea — before heading home late in 1880.