The First Missouri Brigade was an infantry brigade that served in the Confederate States Army during the American Civil War.

It was mostly recruited from members of the Missouri State Guard – a secessionist force formed from the Missouri Volunteer Militia when the allegiance of the state was disputed.

It was initially led and drilled by Lewis Henry Little.

In March 1863, Francis Cockrell took command of the brigade and led it for most of the remaining war.

The unit had its last stand under Col. James McCown at the Battle of Fort Blakeley in April 1865.