Before the war, Jackson worked with his father-in-law, John Sappington, to manufacture and sell patent medicines, in the form of quinine pills, to treat and prevent malaria.

However, in 1861, after the Missouri Convention rejected secession, Jackson secretly planned a secessionist coup in league with the Confederate government.

After the fall of Fort Sumter, South Carolina, in April 1861, Jackson denounced President Abraham Lincoln's call for volunteers and began plotting to seize the U.S. Arsenal in St. Louis.

Jackson fled the state capital, Jefferson City, as Lyon's forces approached and established a rump legislature at Neosho; this body formally voted to secede the following October.

However, continuing Union successes under Gen. Samuel R. Curtis sent the secessionist governor and his followers fleeing again, this time into Arkansas, where they erected a temporary capital at Camden.

Claiborne Jackson continued to work with his brothers after his wife's death, until 1832 and the outbreak of hostilities in the Black Hawk War.

[2] As a young widower, Claiborne Jackson organized, and was elected captain of, a unit of Howard County volunteers for the conflict.

After returning from the war, Jackson decided to make a change, moving to nearby Saline County, where his father-in-law lived.

Through his family connections with Dr. Sappington, Jackson, along with his brother-in-law Meredith M. Marmaduke, became deeply involved with Missouri Democratic Party politics.

He moved to the Howard County seat of Fayette, Missouri—then a center of political power in the state—in 1838 and worked for the local branch of the state bank.

As leader of the pro-slavery Democrats, he headed efforts to defeat US Senator Thomas H. Benton, a powerful politician who was pro-Union.

This likely cost him the chance to be elected governor in his own right (he had served ten months in the role to fill the term following the suicide of Thomas Reynolds.)

During his inaugural address, he declared that Missouri shared a common bond and interest with other states that allowed slavery and could not separate herself from them if the Union should be dissolved.

[1] After the Confederate bombardment of Fort Sumter in South Carolina on April 12–13, President Abraham Lincoln issued a proclamation for the states to call up their militia and provide 75,000 troops to the Federal government to suppress the rebellion.

Jackson responded, Sir: Your dispatch of the 15th instant, making a call on Missouri for four regiments of men for immediate service, has been received.

There can be, I apprehend, no doubt that the men are intended to form a part of the President's army to make war upon the people of the seceded states.

[2]In this period, Jackson was carrying on secret correspondence with Confederate President Jefferson Davis, making plans to take Missouri out of the Union by a military coup.

Governor Jackson's order to assemble the militia was legal according to the Missouri state constitution, if the encampment was intended only for training, and not for offensive action against Federal forces.

On May 10, 1861, Lyon surrounded Camp Jackson with pro-Union volunteer "Home Guards" (mostly drawn from the German immigrants of St. Louis), and took the Militia prisoner.

[8] But, at the same time Governor Jackson had secretly dispatched envoys to CSA President Jefferson Davis and Confederate commanders in Arkansas asking for an immediate invasion of the state.

He promised that the State Guard would cooperate with the Confederate Army in a campaign against Federal forces to effect the "liberation" of St. Louis.

In addition, Lieutenant Governor Thomas C. Reynolds traveled to Richmond, with the agreement of Major General Price, to ask President Davis to order an invasion of the state.

Union forces routed the State Guard, commanded by Jackson's nephew John Sappington Marmaduke, at Boonville on June 17.

Governor to lead troops in battle after Isaac Shelby of Kentucky did so during the War of 1812), and drove back a much smaller Union detachment led by Colonel Franz Sigel.

The same day the convention appointed Hamilton R. Gamble, former Chief Justice of the State Supreme Court, as provisional governor.

Jackson did not recognize their actions; on August 5 he issued a proclamation declaring that Missouri was a free republic, and dissolving all ties with the Union.

Jackson traveled to southern Arkansas in the spring of 1862 to regroup and meet with other wealthy Missouri secessionists who had fled south.

They discussed organizing a new campaign to retake Missouri, but Jackson died of pneumonia and stomach cancer before such actions took place.

[3] His health grew increasingly poor throughout 1862, Jackson traveled to Little Rock, Arkansas, in November of that year for military planning meetings for the aforementioned campaign.

Following the end of the Civil War, he was exhumed, and reinterred in the family Sappington Cemetery of his in-laws in Saline County, Missouri.