Sickles was born in New York City on October 20, 1819. He was the son of George Garrett Sickles and Susan Marsh Sickles. At a young age he kept running away from home. His parents sent him to boarding school when he was 15 years old but he had to leave after a fight with a teacher. He became a printer's helper for a year before returning to New York City. There he developed the habit of hanging out with prostitutes and others with poor reputations. His parents decided he needed a good education and arranged for him to live in the Da Ponte household. Sickles was to be tutored by the elderly Professor Lorenzo Da Ponte. He was already friends with the younger Professor Da Ponte, who was in his 30s at the time. Sickles' parents hoped the friendship would be a good influence on Sickles. Maria Cooke, a young American girl also lived in the household. She was about the same age as Sickles. She was thought to be the natural daughter of the elder Da Ponte who adopted her. Her husband, Antonio Bagioli and their infant daughter, Maria, also lived with the Da Ponte family. At the time she was 3 years old, Sickles was 20. They would marry some 13 years later.
Sickles then studied law at New York University. Afterwards he became involved in politics and was a key figure in the Tammany Hall political machine. He also served as their legal counsel. Through political influence he became the Corporate Council for New York City, Secretary of the United States Legation in London and later a US congressman from New York. In 1852 he married Teresa Bagioli. At the time he was 33 years old and she was 15. Both families were opposed to the marriage at the time. Only a few years later, living in Washington, D.C. as the wife of a congressman, she was described as "more like a schoolgirl than a polished woman of the world" with a "sweet, amicable manner".
Leaving for London, as the assistant to James Buchanan, American minister to Great Britain, he left his young pregnant wife Teresa at home. Instead, as his traveling companion, he brought Fanny White, a notorious prostitute. In London Sickles embarrassed the American delegation on more than one occasion. He refused to drink a toast to Queen Victoria. Another time he introduced Fanny White to the Queen under a false name.
In 1859 Sickles was arrested for murder. His wife had turned to another man for attention. This was Francis Barton Key, son of Francis Scott Key. Sickles repeatedly shot Key in front of his home (which was also in front of the White House. Sickles had a team of lawyers represent him, led by Edwin M. Stanton (future Secretary of State under Abraham Lincoln). Sickles was released on what was the first successful plea of "temporary insanity". Sickles already had a questionable reputation, but this incident made him a pariah. Sickles saw the outbreak of the civil war as an opportunity to save his reputation.
In Congress, Sickles had aligned himself with Southern Democrats and was himself a pro-slavery Democrat. But after the outbreak of the war, Sickles suddenly became Pro-Union. His last session in Congress had ended in March so Sickles was back in New York City practicing law when the war started. In later versions of his motives for joining the Union Army he stated he thought he could best serve the Union by raising a regiment. Republican President Lincoln needed the support of Democrats and apparently saw Sickles as one he could use. After raising a regiment, then a brigade which he named the Excelsior Brigade, Sickles assumed he would be given the rank of brigadier general (a colonel commanded a regiment while a brigadier general commanded a brigade). But officially, he remained a colonel of the first regiment, even though he commanded the entire brigade. New York Governor Edwin D. Morgan decided there were too many regiments from New York City and ordered Sickles to disband some of the regiments. As a result, Sickles would not get a brigadier general's commission. Going around the governor, Sickles went to Washington to meet with Lincoln. The President agreed to enlist the disbanded regiments as United States Volunteers. Finally on July 20, 1861 they received orders to report to Harpers Ferry, West Virginia. In September, Sickles was nominated as a brigadier general of volunteers, but his confirmation was delayed for several months by the United States Senate. Sickles brigade spent most of 1861 in lower Maryland. Sickles frequently visited the Lincolns in Washington during this time. In March 1862, his command was attached to General Joseph Hooker in the Army of the Potomac. That same month, Sickles' brigadier general commission was turned down by the Senate. The Excelsiors saw their first combat that month. Sickles personally led a reconnaissance. Then on April 6, he left the Excelsiors for Washington to protest his not being commissioned a brigadier general. While his unit fought in the Peninsula Campaign, Sickles remained in Washington. Lincoln again nominated him for general and on May 3, 1862 the Senate confirmed him.
On May 24, "brigadier general" Sickles was ordered to report back to Hooker. He was given command of Hooker's 2nd Brigade. Sickles saw his first major engagement at the Battle of Seven Pines. Sickles next saw action at the Seven Days Battles. Hooker's advance did not go well due in part to Sickles' brigade having difficulties moving through the swamps then meeting heavy Confederate resistance. When some of his men broke and ran to the rear, Sickles was only able to get a few to return. Nonetheless, Hooker's report noted Sickles gallantry in trying to rally his men. He did not stay long and missed the Second Battle of Bull Run and the Battle of Antietam, being in New York recruiting men for his brigade. When Ambrose Burnside replaced George B. McClellan as commander of the Army of the Potomac, both Hooker and Sickles were moved up to command larger units. Sickles still had hardly any battlefield experience yet was now leading Hooker's old second division of III Corps. Sickles was busy getting New York newspapers and Washington insiders to promote his image as a battle hardened fighting general.
In December 1862, at the Battle of Fredericksburg, Sickles brigade did not see battle until the third day. He and his troops watched as Union troops fought uphill against Lee's Confederates. After 2:00 p.m. Sickles was finally ordered to the front. Leading his men they found the battle to mostly be over in their section. They secured their position against limited sniper fire and a few Skirmishes but otherwise did not see any fighting.
When Burnside was replaced as commander of the Army of the Potomac, Hooker was moved up to replace him. In the new assignments resulting from the change, and even though he had little battlefield experience, Sickles was given temporary command of III Corps. But again, the Senate did not confirm his promotion to Major General. Finally, on March 9 (with his rank to date back to November 29), the Senate confirmed his promotion. By the end of March Sickles was officially a major general. Unlike earlier battles, at the Battle of Chancellorsville, Sickles saw action. As Sickles observed Confederate general Stonewall Jackson's flanking maneuver, without orders he pushed forward with two-thirds of his corps to go after the Confederates. This left XI Corps on his right completely isolated. Jackson's confederates then made a crushing attack on XI Corps. Sickles leaving his assigned position was a major factor in the Confederate victory. This started a feud between Hooker and Sickles that continued into the Battle of Gettysburg. Hooker blamed Sickles for the defeat at Chancellorsville.