In 1861, after the American Civil War broke out, he joined the Union war effort, taking charge of training new regiments and then engaging the enemy near Cairo, Illinois. In 1862 he fought a series of major battles and captured a Confederate army, earning a reputation as an aggressive general and allowing the Union to seize control of most of Kentucky and Tennessee. In July 1863, after a long complex campaign he captured Vicksburg, captured another Confederate army, and took control of the Mississippi River, splitting the Confederacy and opening the way for more Union victories and conquests. Abraham Lincoln promoted him to the rank of lieutenant general, and gave him charge of all the Union Armies. As Commanding General of the United States Army from 1864 to 1865, Grant confronted Robert E. Lee in a series of very high casualty battles known as the Overland Campaign that ended in a stalemate siege at Petersburg. During the siege, Grant coordinated a series of devastating campaigns launched by William Tecumseh Sherman, Philip Sheridan, and George Thomas. Finally breaking through Lee's trenches at Petersburg, the Union Army captured Richmond, the Confederate capital in April 1865. Lee surrendered to Grant at Appomattox; the Confederacy collapsed and the Civil War ended.

During Reconstruction, Grant remained in command of the Army and implemented the Congressional plans to reoccupy the South and hold new elections in 1867 with black voters that gave Republicans control of the Southern states. Enormously popular in the North after the Union's victory, he was elected to the presidency in 1868. Reelected in 1872, he became the first president to serve two full terms since Andrew Jackson did so forty years earlier. As president, he led Reconstruction by signing and enforcing civil rights laws and fighting Ku Klux Klan violence. He helped rebuild the Republican Party in the South, an effort that resulted in the election of African Americans to Congress and state governments for the first time. Despite these civil rights accomplishments, Grant's presidency was marred by economic turmoil and multiple scandals. His response to the Panic of 1873 and the severe depression that followed was heavily criticized. His low standards in Cabinet and federal appointments and lack of accountability generated corruption and bribery in seven government departments. In 1876, his reputation was severely damaged by the graft trials of the Whiskey Ring. He left office at the low point of his popularity.

After leaving office, Grant embarked on a two-year world tour that was received favorably with many royal receptions. In 1880 he made an unsuccessful bid for a third presidential term. In 1884, broke and dying of cancer, he wrote his enormously successful memoirs. Historians have ranked his Administration poorly due to tolerance of corruption. His presidential reputation has improved among scholars impressed by the Administration's support for civil rights for freed slaves.

Hiram Ulysses Grant was born in Point Pleasant, Ohio on April 27, 1822 to Jesse Root Grant (1794–1873), a tanner, and Hannah Simpson Grant (1798–1883), both Pennsylvania natives. In the fall of 1823, the family moved to the village of Georgetown in Brown County, Ohio. Raised a Methodist, although not an official member of the church, he prayed in private and opposed religious pretentiousness. At the age of 17, the young Ulysses entered the United States Military Academy (USMA) at West Point, New York, secured by Congressman Thomas L. Hamer's nomination. Hamer mistakenly nominated him as "Ulysses S. Grant of Ohio." At West Point he adopted this name with a middle initial only. His nickname became "Sam" among army colleagues at the academy since the initials "U.S." stood for "Uncle Sam". He graduated from West Point in 1843, ranking 21st in a class of 39. At the academy, he established a reputation as a fearless and expert horseman, setting an equestrian high jump record that lasted almost 25 years. Although naturally suited for cavalry, he was assigned to duty as a regimental quartermaster, achieving the rank of lieutenant, managing supplies and equipment.

During the Mexican American War (1846–1848), Lieutenant Grant served under Generals Zachary Taylor and Winfield Scott. Although assigned as a quartermaster, he got close enough to the front lines to see action, participating in the battles of Resaca de la Palma, Palo Alto, Monterrey, and Veracruz. At Monterrey, he carried a dispatch voluntarily on horseback through a sniper-lined street. He was twice brevetted for bravery: at Molino del Rey and Chapultepec. He was a remarkably close observer of the war, learning to judge the actions of colonels and generals, particularly admiring how Zachary Taylor campaigned. At the time he felt that the war was a wrongful one and believed that territorial gains were designed to spread slavery throughout the nation, writing in 1883, "I was bitterly opposed to the measure, and to this day, regard the war, which resulted, as one of the most unjust ever waged by a stronger against a weaker nation."

On August 22, 1848, Grant married Julia Boggs Dent (1826–1902), the daughter of a slave owner. Together, they had four children: Frederick Dent Grant, Ulysses S. "Buck" Grant, Jr., Ellen Wrenshall "Nellie" Grant, and Jesse Root Grant.

Lieutenant Grant remained in the army and was assigned to several different posts. He was sent west overseas to Fort Vancouver in the Washington Territory in 1852, initially landing in San Francisco during the height of the California gold rush. Julia was eight months pregnant with their second child and could not accompany him because a lieutenant's salary, at the time, would not support a family on the frontier. The journey proved to be a horrid ordeal and Grant narrowly escaped a cholera epidemic while traveling overland through Panama. At Fort Vancouver he served as quartermaster of the 4th Infantry Regiment. In 1854, he was promoted to captain, one of only 50 still on active duty, and assigned to command Company F, 4th Infantry, at Fort Humboldt, on the northwest California coast. Without explanation, he abruptly resigned from the Army with little notice on July 31, 1854. Commanding officer at Fort Humbolt, Bvt. Lt. Col. Robert C. Buchanan, had learned that Grant was intoxicated off duty while seated at the pay officer's table. Buchanan gave him an ultimatum and told him to leave the Army either by court-martial or resignation. Whether the threat of court-martial by Buchanan was justifiable, Grant decided to resign, the War Department having stated on his record, "Nothing stands against his good name." Rumors, however, persisted in the regular army of Grant's intemperance.

A civilian at age 32, Grant struggled through seven financially lean years. From 1854 to 1858, he labored on a family farm near St. Louis, Missouri, using slaves owned by Julia's father, but it did not prosper. He bought one of these slaves in 1858. From 1858–1859, he was a bill collector in St. Louis. In 1860, after many failed business pursuits, he was given a job as an assistant in his father's tannery in Galena, Illinois. The leather shop, "Grant & Perkins", sold harnesses, saddles, and other leather goods and purchased hides from farmers in the prosperous Galena area. He moved his family to Galena and lived in a brick house before the Civil War broke out.

Up until the outbreak of the Civil War, Grant kept any political opinions private and never endorsed any candidate running for public office. He also, at this time, had no animosity toward slavery. His father-in-law was a prominent Democrat in St. Louis, a fact that contributed to a failed attempt to become county engineer in 1859. In the 1856 presidential election, he voted for the Democratic candidate, James Buchanan, to prevent secession and because "I knew Frémont", the Republican presidential candidate. In 1860, he favored Democratic presidential candidate Stephen A. Douglas over Abraham Lincoln, but did not vote. His own father, Jesse Root, was a prominent Republican in Galena. It was during the Civil War that his political sympathies coincided with the Republicans' aggressive prosecution of the war. In 1864, his patron Congressman Elihu B. Washburne used Grant's private letters as campaign literature for Lincoln's reelection. In 1868 Grant, affiliated with the Radical Republicans, was nominated as the Republican presidential candidate.

Appointed July 31, 1861