In 1861 Chalmers was appointed as colonel of the 9th Mississippi Infantry. For the first year he served in Florida. In February 1862 he was promoted to brigadier general and moved to Tennessee. He fought at the Battle of Shiloh. He participated in the invasion of Kentucky and at the Battle of Murfreesboro. In November 1862, at the Battle of Munfordville, Kentucky, he distinguished himself with his demand for the surrender of the Union garrison. Transferring to the cavalry under General Nathan B. Forrest, Chalmers served in North Mississippi, Kentucky, and in west Tennessee. In November 1863 he led a cavalry division into action at Colliersville, Tennessee. In the following spring in April 1864, he commanded the Confederate force on the field in the attack on Fort Pillow, Tennessee. Finally, he participated in the 1864 campaign against Nashville.