The history of the area that is now the U.S. state of Louisiana, can be traced back thousands of years to when it was occupied by indigenous peoples. The first indications of permanent settlement, ushering in the Archaic period, appear about 5,500 years ago. The area that is now Louisiana formed part of the Eastern Agricultural Complex. The Marksville culture emerged about 2,000 years ago out of the earlier Tchefuncte culture. It is considered ancestral to the Natchez and Taensa peoples. Around the year 800 AD, the Mississippian culture emerged from the Woodland period. The emergence of the Southeastern Ceremonial Complex coincides with the adoption of maize agriculture and chiefdom-level complex social organization beginning in circa 1200 AD. The Mississippian culture mostly disappeared around the 16th century, with the exception of some Natchez communities that maintained Mississippian cultural practices into the 1700s.

European influence began in the 1500s, and La Louisiane (named after Louis XIV of France) became a colony of the Kingdom of France in 1682, before passing to Spain in 1763. Louisiana was formed in part of the became part of the Louisiana Purchase from France in 1803. The U.S. would divide that area into two territories, the Territory of Orleans, which formed what would become the boundaries of Louisiana, and the District of Louisiana. Louisiana was admitted as the 18th state of the United States on April 30, 1812. The final major battle in the War of 1812, the Battle of New Orleans, was fought in Louisiana and resulted in a U.S. victory.

Antebellum Louisiana was a leading slave state, where by 1860, 47% of the population was enslaved. Louisiana seceded from the Union on 26 January 1861, joining the Confederate States of America. New Orleans, the largest city in the entire South at the time, and strategically important port city, was taken by Union troops on 25 April 1862. After the defeat of the Confederate Army in 1865, Louisiana would enter the Reconstruction era (18651877). During Reconstruction, Louisiana was subject to U.S. Army occupation, as part of the Fifth Military District.

Following Reconstruction in the 1870s, white Democrats had regained political control in the state. In 1896, the U.S. Supreme Court decision in the Plessy v. Ferguson case ruled that "separate but equal" facilities were constitutional. The lawsuit stemmed from 1892 when Homer Plessy, a mixed-race resident of New Orleans, violated Louisiana's Separate Car Act of 1890, which required "equal, but separate" railroad accommodations for white and non-white passengers. This court decision upheld Jim Crow laws that had started to form in the 1870s. In 1898, white Democrats in the Louisiana state legislature passed a new disfranchising constitution, whose effects were immediate and long-lasting. The disfranchisement of African Americans in the state did not end until national legislation passed during the Civil Rights Movement in the 1960s.

In the early-to-mid 20th century, many African Americans would leave the state in the Great Migration. They moved to mainly urban areas in the North and Midwest. The Great Depression of the 1930s would hit the states economy hard, as mostly agricultural state at the time, farm prices had dropped to all-time lows. In the states urban areas such as New Orleans, many warehouses and businesses had closed, leaving many unemployed. The Federal Emergency Relief Administration would help flow money into the state, providing employment opportunities for Louisiana projects. World War II would help accelerate the industrialization of Louisiana's economy and provide further economic growth. In the 1950s and 1960s, the Civil Rights Movement had started to gain national attention, and with the passing of the Civil Rights Act of 1964 and Voting Rights Act of 1965, disfranchisement of African Americans in the state had ended.

In the late 20th Century, Louisiana saw rapid industrialization and rise of economic markets such as oil refineries, petrochemical plants, foundries, along with industries of produce foods, fishing, transportation equipment, and electronic equipment. Tourism also became important to the Louisiana economy, with Mardi Gras becoming a known major celebration held annually since 1838. In 2005, Hurricane Katrina struck Louisiana and surrounding areas in the Gulf of Mexico, resulting in major damages. A $15 billion dollar new levee system built in New Orleans would take place from 2006 to 2011.

The American Civil War (April 12, 1861 – May 9, 1865; also known by other names) was a civil war in the United States between the Union (states that remained loyal to the federal union, or "the North") and the Confederacy (states that voted to secede, or "the South"). The central cause of the war was the status of slavery, especially the expansion of slavery into territories acquired as a result of the Louisiana Purchase and the Mexican–American War. On the eve of the Civil War in 1860, four million of the 32 million Americans (~13%) were enslaved black people, almost all in the South.The practice of slavery in the United States was one of the key political issues of the 19th century. Decades of political unrest over slavery led up to the Civil War. Disunion came after Abraham Lincoln won the 1860 United States presidential election on an anti-slavery expansion platform. An initial seven southern slave states declared their secession from the country to form the Confederacy. Confederate forces seized federal forts within territory they claimed. The last-minute Crittenden Compromise tried to avert conflict but failed; both sides prepared for war. Fighting broke out in April 1861 when the Confederate army began the Battle of Fort Sumter in South Carolina, just over a month after the first inauguration of Abraham Lincoln. The Confederacy grew to control at least a majority of territory in eleven states (out of the 34 U.S. states in February 1861), and asserted claims to two more. Both sides raised large volunteer and conscription armies. Four years of intense combat, mostly in the South, ensued.

During 1861–1862 in the war's Western Theater, the Union made significant permanent gains—though in the war's Eastern Theater the conflict was inconclusive. On January 1, 1863, Lincoln issued the Emancipation Proclamation, which made ending slavery a war goal, declaring all persons held as slaves in states in rebellion "forever free." To the west, the Union destroyed the Confederate river navy by the summer of 1862, then much of its western armies, and seized New Orleans. The successful 1863 Union siege of Vicksburg split the Confederacy in two at the Mississippi River. In 1863, Confederate General Robert E. Lee's incursion north ended at the Battle of Gettysburg. Western successes led to General Ulysses S. Grant's command of all Union armies in 1864. Inflicting an ever-tightening naval blockade of Confederate ports, the Union marshaled resources and manpower to attack the Confederacy from all directions. This led to the fall of Atlanta in 1864 to Union General William Tecumseh Sherman and his march to the sea. The last significant battles raged around the ten-month Siege of Petersburg, gateway to the Confederate capital of Richmond.

The Civil War effectively ended on April 9, 1865, when Confederate General Lee surrendered to Union General Grant at the Battle of Appomattox Court House, after Lee had abandoned Petersburg and Richmond. Confederate generals throughout the Confederate army followed suit. The conclusion of the American Civil War lacks a clean end date: land forces continued surrendering until June 23. By the end of the war, much of the South's infrastructure was destroyed, especially its railroads. The Confederacy collapsed, slavery was abolished, and four million enslaved black people were freed. The war-torn nation then entered the Reconstruction era in a partially successful attempt to rebuild the country and grant civil rights to freed slaves.

The Civil War is one of the most studied and written about episodes in the history of the United States. It remains the subject of cultural and historiographical debate. Of particular interest is the persisting myth of the Lost Cause of the Confederacy. The American Civil War was among the earliest to use industrial warfare. Railroads, the telegraph, steamships, the ironclad warship, and mass-produced weapons saw wide use. In total the war left between 620,000 and 750,000 soldiers dead, along with an undetermined number of civilian casualties. President Lincoln was assassinated just five days after Lee's surrender. The Civil War remains the deadliest military conflict in American history. The technology and brutality of the Civil War foreshadowed the coming World Wars.