Many issues began to divide the Northern and Southern states. Above all, the North and the South clashed over slavery. Many Northerners who were against slavery joined the new Republican Party. When Republican candidate Abraham Lincoln won the 1860 presidential election, Southern leaders carried out their threats to secede and formed the Confederate States of America. Many Texans urged Governor Houston to call for a convention to consider the secession of Texas. He was against secession and refused to call the convention.

In January 1861, citizens who favored secession set up their own Texas Secession Convention in Austin. In February 1861, Texas became the seventh state to withdraw from the Union. Houston was removed as governor, and Lieutenant Governor Edward Clark assumed the post.

About 60,000 Texans served in the armed forces of the Confederacy. Many Civil War officers came from Texas, including Albert Sidney Johnston. Hood's Texas Brigade and Terry's Texas Rangers were among the better-known units serving east of the Mississippi River. About 2,000 Texans joined the Union army.

Texas suffered less physical damage than did other Confederate states because few battles were fought in the state. The war brought economic changes, however. The Union blockade of Southern ports stopped many goods from reaching Texas, and the people made many sacrifices.

After four long years of fighting—on April 9, 1865—Confederate forces surrendered. The last land battle of the Civil War took place on May 13, 1865, near Brownsville. The state government collapsed, and Texas faced the task of rejoining the Union.