During the American Civil War, the Union Army seized control of the line and used the western section to supply its occupation force in Little Rock.

The railroad, though incomplete in its central section, allowed travelers to go from Little Rock to Memphis an entire day faster than by steamboat alone.

[1] During the early part of the Civil War, Confederate soldiers were often transferred to Memphis via the eastern section of the M&LR.

The railroad desired to complete construction of the central section, but the Confederate government was unable to fund the effort.

By August 18, Steele's combined force of 13,000 troops (soon reinforced to 14,500) and 57 artillery pieces reached DeValls Bluff.

Confederates launched raids to block the vital railroad, but these were unable to interrupt the supply route for long periods.

The central and eastern sections were plagued by floods, so that in some places the track was anchored to trees on the upstream side of the roadbed.

In 1900, another sale was made to the Choctaw, Oklahoma and Gulf Railroad before it finally ended up as part of the Rock Island.