The prairie's strategic importance was clear to both sides. To the west lay Washington, Arkansas, which had served as the Confederate state capital since the fall of Little Rock in September 1863. To the east lay the fortified city of Camden. To the south, the Red River led to Shreveport. Whoever controlled Prairie D'Ane controlled the crossroads. The Confederates recognized this and built extensive earthen and log breastworks along the prairie's northern edge, most of it constructed with slave labor. But the wide-open terrain posed a dilemma for the defenders: the same flat ground that offered clear fields of fire for their artillery also gave an attacking force ample room to maneuver and outflank fixed positions. Confederate forces under Major General Sterling Price, consisting primarily of mounted Arkansas and Missouri regiments under Generals James Fagan, John Marmaduke, and Samuel Maxey, dug in and waited.

The first blood was drawn at a crossing of the Little Missouri River on April 2-4. Lieutenant Colonel F.M. Drake, commanding just three companies of the 36th Iowa Infantry and three companies of the 43rd Indiana Infantry -- fewer than 400 men total -- held a forward position in dense timber south of the river against two full brigades under Marmaduke. When brigade commander McLean ordered a general retreat to the riverbank, Drake defied the order, telling his six companies to "Stand Fast." For two hours, the outnumbered Federals were pushed steadily backward as Marmaduke brought up artillery and raked the woods with grapeshot. When the 43rd Indiana's flank finally collapsed, Colonel Kittredge advanced his remaining seven companies of the 36th Iowa to the edge of an open field, ordered his men to lie down behind a slight ridge, and waited. When the Confederates charged across the field to capture the Union guns, Kittredge's men rose and fired devastating volleys with their newly issued Springfield .58 caliber rifled muskets. The attack broke.

Steele's VII Corps had left Little Rock with inadequate provisions, and the men marched on half-rations through rain-soaked country, finding little to forage along the way. Disease had already gutted the ranks: typhoid, measles, malaria, influenza, and chronic diarrhea had put entire divisions on the sick list during previous service in the Arkansas Delta. When Steele's forces reached the northern edge of Prairie D'Ane around April 10, they attacked with artillery, cavalry, and infantry skirmishers, driving the Confederate line back about a mile. Skirmishing continued through April 11. But Steele's intelligence was growing darker. Rumors filtered in that Banks's Red River force had been repelled. Steele -- who had doubted the campaign's wisdom from the start and had delayed his departure until receiving a blunt direct order from Ulysses S. Grant -- now faced a grim calculus. Deep in enemy territory on quarter rations, with exhausted mules and mud-clogged roads, he decided to abandon the advance on Washington and divert east to Camden, hoping to find provisions.

Steele ordered General John Thayer's Frontier Division to feint toward Washington, drawing Confederate attention while the main force slipped east on the Camden Road. The ruse was quickly discovered, leading to a rear-guard action at the hamlet of Moscow on the prairie's southeast edge. Steele reached Camden with minimal opposition but found meager supplies and confirmation that Banks had indeed been defeated. What followed was catastrophe. On April 18, Confederates ambushed a Union supply train at Poison Springs, destroying nearly 500 wagons and killing 1,200 mules. On April 25, another ambush at Marks' Mills devastated a second supply column. Steele had no choice but to retreat north to save his army. The VII Corps left Camden before dawn on April 27 and fought a running battle all the way to the Saline River, where the campaign ended at the Battle of Jenkins Ferry on April 29-30. Today, 811 acres of the Prairie D'Ane battlefield have been preserved by the American Battlefield Trust. The site is listed on the National Register of Historic Places as part of the Camden Expedition Sites National Historic Landmark.