Originally commanded by Colonel John S. Bowen, the regiment fought at the Battle of Shiloh, where it was engaged near the Peach Orchard on April 6, 1862.

On April 7, during the Union counterattacks at Shiloh, the regiment was instrumental in preventing the Washington Artillery from being captured.

[3] After the Battle of Fort Donelson in early 1862, the regiment participated in the destruction of Confederate property during the abandonment of Nashville, Tennessee.

[5] On April 6, the first day of the Battle of Shiloh, the 1st Missouri and the rest of Bowen's brigade attacked a Union defensive position known as the Peach Orchard.

[7] On April 7, the 1st Missouri participated in the Confederate defense against Union counterattacks, and played a significant role in preventing the capture of a portion of the Washington Artillery.

[2] After the Confederates abandoned Corinth in the summer of 1862, the 1st Missouri was transferred to the Vicksburg, Mississippi, area.

The regiment, as well as the rest of Bowen's brigade, was expected to be part of the Confederate assault at the Battle of Baton Rouge, but arrived too late for the fighting.

[4] By early October, the 1st Missouri was part of Major General Earl van Dorn's Army of West Tennessee.

[9] On October 3, at the Second Battle of Corinth, the 1st Missouri was part of the Confederate assault on the Union's outer defensive works.

The 1st Missouri outflanked a Union position commanded by Brigadier General John McArthur, helping Moore's brigade break the line.

The 1st Missouri outflanked the 15th Iowa Infantry, which, accompanied by Moore's primary assault on Crocker's line, led to the collapse of the Union position.

[12] The next day, Bowen's brigade was only briefly engaged during Confederate attacks on the stronger interior Union position, as Lovell's division was mostly inactive on October 4.