In March of 1863 the newly rechristened Arizona joined Admiral David Farragut's West Coast Blockading Squadron whose mission was part of the Union's Anaconda strategy designed to squeeze the South's ability to import armaments and other goods that the Confederacy required to win the war. Acting Lieutenant Daniel P. Upton, son of a wealthy and influential Boston merchant and ship builder, assumed command of the Arizona.
The addition of the Arizona to Farragut's gunboat fleet was timely as his recent attempt to penetrate Confederate held territory north of Port Hudson had failed. Arizona played an important role in strengthening Farragut's drastically reduced force and opening up communications between its commander and the rest of his squadron. From New Orleans, she proceeded to Berwick Bay to join a naval force commanded by Comdr. Augustus P. Cook which, in cooperation with troops commanded by Major General Nathaniel P. Banks, was operating in the swampy backwaters of the Louisiana lowlands west of the Mississippi.
On 14 April, while carrying army units, she, Estrella, and Calhoun attacked CSS Queen of the West on Grand Gulf, a wide and still stretch of the Atchafalaya River. A shell from Calhoun set fire to cotton which her Southern captors had loaded on that former Ellet ram and blew up her boiler. The burning cotton-clad drifted downstream for several hours before running aground and exploding.
Six days later, Clifton and Calhoun joined the same force and, working with four companies of Union infantry, took Fort Burton, a Southern battery consisting of two old siege guns implaced at Butte La Rose, La. This victory opened for Union ships a passage—through Atchafalaya Bay and the River of the same name—connecting the gulf with the Red and Mississippi Rivers. Thus, Farragut could bypass Port Hudson with supplies, messages, and ships.
After this path was clear, Arizona entered the Red River and descended it to its mouth where she met Hartford, Farragut's flagship. On 3 May, she was part of a three-ship reconnaissance force that ascended the Red River until it encountered heavy fire from two large Confederate steamers, Grand Duke and Mary T., supported by Southern shore batteries and snipers. Since the narrow channel prevented their maneuvering to bring their broadsides to bear on their attackers, the Union ships were compelled to retire.
As they descended, the Northern vessels met a large force led by Rear Admiral David Dixon Porter who ordered Arizona and Estella to join him in a much more powerful drive up the Red River. .
The next morning, Porter's force arrived at Fort DeRussy—an uncompleted stronghold the South had been building on the banks of the river—and found it abandoned. After partially destroying the fortifications, Porter continued on up stream to Alexandria which surrendered without resistance. Before Porter left the river, Arizona took part in a reconnaissance of the Black River, a tributary of the Red. On 10 May, she joined in an attack on Fort Beauregard at Harrisonburg, La., on the Ouachita River.
Following her return to the Mississippi, Arizona supported operations against Port Hudson which finally fell on 9 July—five days after the surrender of Vicksburg—removing the last Southern hold on the river and finally cutting the Confederacy in two. The Arizona then returned to New Orleans for repairs. During this work, Acting Master Howard Tibbito relieved Upton in command of the side-wheeler.
On 4 September, Arizona departed New Orleans and proceeded to Southwest Pass to embark 180 sharpshooters to be distributed among Clifton, Sachem, and herself in a forthcoming attack on Sabine Pass, Tex. She next proceeded to Atchafalaya Bay where she met her consorts and a group of Army transports, distributed her sharpshooters, and continued on to Sabine Pass.
On the morning of 8 September, the combined force crossed the bar and then split, with Sachem and Arizona advancing up the Louisiana (right) channel and Clifton and Granite City moving forward through the Texas (left) channel. When they arrived within range of the Confederate batteries they opened fire preparatory to landing the troops. The Southern gunners did not reply until the gunboats were within close range, but then countered with a devastating cannonade. A shot through her boiler totally disabled Sachem; another carried away Clifton's, wheel rope, causing her to run aground under the Confederate guns. Crocker—who commanded Clifton as well as the whole naval force—fought his ship until, with 10 men killed and nine others wounded, he deemed it his duty "to stop the slaughter by showing the white flag. ..." After flooding her magazine to prevent its exploding, Sachem also surrendered and was taken under tow by CSS Uncle Ben. With the loss of Clifton's and Sachem's firepower, the two remaining gunboats and troop transports recrossed the bar and departed for New Orleans.
The Sabine Pass expedition had, in the words of Commodore H. H. Bell, "totally failed." Nevertheless, Major General Banks reported: "In all respects the cooperation of the naval authorities has been hearty and efficient. ..."