Under the command of Joshua R. Sands, Vixen first saw action on 16 October 1846 when she participated in the unsuccessful attempt to take Alvarado, Mexico, the most important Mexican port east of Vera Cruz.

Commodore Matthew C. Perry assumed command of the gunboat and, with the schooners Bonita and USRC Forward in tow, dashed across the bar and captured the Mexican flotilla defending the port.

[3] After Mexican defenders rejected peace overtures, the American squadron attacked the city on the 23rd; and, two days later, Spitfire and Vixen made a daring and visually spectacular close range assault upon defensive fortifications ashore.

This stunning victory enabled General Winfield Scott to march on Mexico City by the shortest overland route and, as such, was the decisive action of the Mexican War.

The gunboat was temporarily decommissioned at Pensacola, Florida, in 1853 after numerous fatal outbreaks of yellow fever swept her and underwent further repairs at the Brooklyn Navy Yard in 1854.