The First Battle of Newtonia was fought on September 30, 1862, between Confederate soldiers commanded by Colonel Douglas H. Cooper and a Union column commanded by Brigadier General Frederick Salomon near Newtonia, Missouri, during the American Civil War. Cooper's force had moved into southwestern Missouri, and encamped near the town of Newtonia. The Confederate column was composed mostly of cavalry led by Colonel Joseph O. Shelby and a brigade of Native Americans. A Union force commanded by Brigadier General James G. Blunt moved to intercept Cooper's force. Blunt's advance force, led by Salomon, reached the vicinity of Newtonia on September 29, and attacked Cooper's position on September 30. A Union probing force commanded by Colonel Edward Lynde was driven out of Newtonia by Cooper's forces on the morning of the 30th.

Both sides brought up further reinforcements, and seesaw fighting took place during much of the afternoon. Shortly before nightfall, Cooper's Confederates made an all-out attack against the Union line; this led Salomon to withdraw from the field. Militia commanded by Colonel George Hall covered the Union retreat, although Confederate artillery fire struck the retreating forces. This panicked some of Salomon's men, and the retreat turned into a disorderly rout. Union casualties are variously reported as either 245 or over 400, and Confederate casualties were 78. Blunt's full division began advancing towards Newtonia in early October, leading Cooper to abandon Missouri. A portion of the battlefield was listed on the National Register of Historic Places in 2004 as the First Battle of Newtonia Historic District.

As the United States matured during the early 19th century, a large cultural divide developed between the northern states and the southern states over the issue of slavery. By the time of the 1860 United States Presidential Election, slavery had become one of the defining features of southern culture, with the ideology of states' rights being used to defend the institution. With the population of the industrializing North coming to exceed that of the South, the balance of power began to shift, and many southerners decided that secession was the only way to preserve slavery, especially after Abraham Lincoln was elected president in 1860. Lincoln's candidacy was regionally successful, as much of his support was from the northern states, while he received no electoral votes from the Deep South. Many southerners rejected the legitimacy of Lincoln's election, and promoted secession. On December 20, the state of South Carolina seceded, and the states of Mississippi, Florida, Alabama, Georgia, Louisiana, and Texas followed suit in early 1861. On February 4, the seceding states formed the Confederate States of America; Jefferson Davis became the nascent nation's president.

In Charleston Harbor, South Carolina, the important military installation of Fort Sumter was still held by a Union Army garrison. On the morning of April 12, the Confederates fired on Fort Sumter, beginning the American Civil War. The fort surrendered on April 13. Shortly after Fort Sumter was attacked, Lincoln requested that the states remaining in the Union provide 75,000 volunteers for the war effort. In the coming weeks, the states of Virginia, North Carolina, Tennessee, and Arkansas joined the Confederacy. A Union army commanded by Brigadier General Irvin McDowell moved south into Virginia and attacked two Confederate armies commanded by Brigadier Generals P. G. T. Beauregard and Joseph E. Johnston on July 21. In the ensuing First Battle of Bull Run, the Union army was routed.

Meanwhile, the population of the state of Missouri was badly divided. While Governor Claiborne F. Jackson and the Missouri State Guard, a militia organization, supported the Confederacy, Brigadier General Nathaniel Lyon, commander of the St. Louis Arsenal, supported the Union. Lyon drove Jackson and the Missouri State Guard, which was commanded by Major General Sterling Price, into southwestern Missouri, where they were joined by Brigadier General Ben McCulloch's Confederate force. Lyon attacked Price and McCulloch's combined camp on August 10 in the Battle of Wilson's Creek; Lyon was killed and his army defeated. Price then moved north with the Missouri State Guard in a campaign that culminated in the capture of Lexington in September. However, Union forces concentrated against Price, who then retreated back into southwestern Missouri. In February 1862, Union Brigadier General Samuel R. Curtis advanced against Price's position, causing the Confederates to abandon Missouri and enter Arkansas. In March, Price, McCulloch, and Major General Earl Van Dorn joined forces. Under the command of Van Dorn, the Confederates attacked Curtis at the Battle of Pea Ridge on March 7 and 8 but were repulsed. Pea Ridge and another Union victory at the Battle of Island Number Ten led the Union high command to feel secure enough to proclaim that "[there was] no Rebel flag now flying in Missouri".

This state of affairs did not last long. Price sent some of his troops into Missouri to obtain supplies and recruit new volunteers. The state was also raided by Confederate forces including the command of Colonel Joseph C. Porter, and was plagued by guerrilla attacks from bushwhackers including William Quantrill. At one point Quantrill's guerrillas combined with a regular Confederate force commanded by Colonel John T. Hughes. This combined force defeated a Union force at the First Battle of Independence on August 11. Union forces suffered another defeat on August 15, at the Battle of Lone Jack. The resurgence in Confederate activity was an embarrassment to the commander of the Union's Department of the Missouri, Brigadier General John M. Schofield, who was replaced by Curtis and relegated to the command of the Army of the Frontier.

This period of increased Confederate activity in Missouri was related to Major General Thomas C. Hindman's efforts to rebuild Confederate strength in Arkansas. While Hindman was successful in forging an army in an underdeveloped region, his methods were unpopular with prominent Arkansas civilians and he was replaced by Major General Theophilus H. Holmes. Hindman retained a field command under Holmes and pushed a 6,000-man force into northwestern Arkansas and the southwestern portion of Missouri. Cavalry forces under Colonel Douglas H. Cooper were positioned in Missouri, with Hindman's infantry component still in Arkansas near Elkhorn Tavern under the command of James S. Rains, a brigadier general in the Missouri State Guard. Hindman himself had been recalled to Little Rock, Arkansas, by Holmes. Cooper's force included the cavalry of Colonel Joseph O. Shelby's Iron Brigade, and a brigade of Confederate-sympathizing Native Americans. A Union force commanded by Brigadier General James G. Blunt and spearheaded by Brigadier General Frederick Salomon began moving south to confront the Confederates.

Cooper sent a scouting force to the Newtonia area on September 27. Commanded by Colonel Trezevant C. Hawpe, it was composed of the 31st Texas Cavalry Regiment and the 1st Cherokee Battalion. Hawpe determined that Newtonia, which was a communications hub, would be a good encampment and had his troops begin operating a grist mill to produce flour. After receiving Hawpe's appraisal of Newtonia's potential as a military base, Cooper ordered him to remain in Newtonia and reinforced him with Captain Joseph Bledsoe's Missouri Battery. On September 28, Hawpe was informed by local residents that Union troops were advancing towards Granby, which was about 7 miles (11 km) away, but Confederate scouts found no evidence of this movement. Meanwhile, Union forces began concentrating in southwestern Missouri. On September 28, two brigades under Colonel William A. Weer and Salomon rendezvoused at Sarcoxie, which was over 10 miles (16 km) from Newtonia; Colonel James Totten's division was expected to leave Springfield on September 29.