The first engagement in the Wheatfield was actually that of Anderson's brigade (Hood's division) attacking the 17th Maine of Trobriand's brigade, a spillover from Hood's attack on Houck's Ridge. Although under pressure and with its neighboring regiments on Stony Hill withdrawing, the 17th Maine held its position behind a low stone wall with the assistance of Winslow's battery, and Anderson fell back.

By 5:30 p.m., when the first of Kershaw's regiments neared the Rose farmhouse, Stony Hill had been reinforced by two brigades of the 1st Division, V Corps, under Brig. Gen. James Barnes, those of Cols. William S. Tilton and Jacob B. Sweitzer. Kershaw's men placed great pressure on the 17th Maine, but it continued to hold. For some reason, however, Barnes withdrew his understrength division about 300 yards (270 m) to the north—without consultation with Birney's men—to a new position near the Wheatfield Road. Trobriand and the 17th Maine had to follow suit, and the Confederates seized Stony Hill and streamed into the Wheatfield.

Earlier that afternoon, as Meade realized the folly of Sickles's movement, he ordered Hancock to send a division from the II Corps to reinforce the III Corps. Hancock sent the 1st Division under Brig. Gen. John C. Caldwell from its reserve position behind Cemetery Ridge. It arrived at about 6 p.m. and three brigades, under Cols. Samuel K. Zook, Patrick Kelly (the Irish Brigade), and Edward E. Cross moved forward; the fourth brigade, under Col. John R. Brooke, was in reserve. Zook and Kelly drove the Confederates from Stony Hill, and Cross cleared the Wheatfield, pushing Kershaw's men back to the edge of Rose Woods. Both Zook and Cross were mortally wounded in leading their brigades through these assaults, as was Confederate Semmes. When Cross's men had exhausted their ammunition, Caldwell ordered Brooke to relieve them. By this time, however, the Union position in the Peach Orchard had collapsed (see next section), and Wofford's assault continued down the Wheatfield Road, taking Stony Hill and flanking the Union forces in the Wheatfield. Brooke's brigade in Rose Woods had to retreat in some disorder. Sweitzer's brigade was sent in to delay the Confederate assault, and they did this effectively in vicious hand-to-hand combat.

Additional Union troops had arrived by this time. The 2nd Division of the V corps, under Brig. Gen. Romeyn B. Ayres, was known as the "Regular Division" because two of its three brigades were composed entirely of U.S. Army (regular army) troops, not state volunteers. (The brigade of volunteers, under Brig. Gen. Stephen H. Weed, was already engaged on Little Round Top, so only the regular army brigades arrived at the Wheatfield.) In their advance across the Valley of Death they had come under heavy fire from Confederate sharpshooters in Devil's Den. As the regulars advanced, the Confederates swarmed over Stony Hill and through Rose Woods, flanking the newly arrived brigades. The regulars retreated back to the relative safety of Little Round Top in good order, despite taking heavy casualties and pursuing Confederates.

This final Confederate assault through the Wheatfield continued past Houck's Ridge into the Valley of Death at about 7:30 p.m. The brigades of Anderson, Semmes, and Kershaw were exhausted from hours of combat in the summer heat and advanced east with units jumbled up together. Wofford's brigade followed to the left along the Wheatfield Road. As they reached the northern shoulder of Little Round Top, they were met with a counterattack from the 3rd Division (the Pennsylvania Reserves) of the V Corps, under Brig. Gen. Samuel W. Crawford. The brigade of Col. William McCandless, including a company from the Gettysburg area, spearheaded the attack and drove the exhausted Confederates back beyond the Wheatfield to Stony Hill. Realizing that his troops were too far advanced and exposed, Crawford pulled the brigade back to the east edge of the Wheatfield.

The bloody Wheatfield remained quiet for the rest of the battle. But it took a heavy toll on the men who traded possession back-and-forth. The Confederates had fought six brigades against 13 (somewhat smaller) Federal brigades, and of the 20,444 men engaged, about 30% were casualties. Some of the wounded managed to crawl to Plum Run but could not cross it. The river ran red with their blood.