In the election returns, Breckinridge finished second in the Electoral College and third in the popular vote. Republican candidate Abraham Lincoln won the election and most of the states which Breckinridge had carried attempted to secede in protest. Breckinridge offered his services to the Confederate Army and eventually won the rank of major general. (On the same day that he ran for President, Breckinridge also ran for and won a Senate seat in Kentucky. He took the oath of office as a US Senator and did not formally resign his seat despite joining the Confederate cause. In December 1861 he was expelled from the Senate by resolution as punishment for supporting the nation's enemies in violation of the Senatorial oath of office.)
Breckinridge served with the Army of Tennessee through the Chattanooga campaign, and joined a long list of Confederate generals who found it difficult to serve alongside Braxton Bragg. In 1864 he was transferred to the Eastern Theater where he commanded Rebel forces in the Shenandoah Valley where he won the Battle of New Market. His command was soon sent to reinforce the Army of Northern Virginia in time for the Battle of Cold Harbor. He also took part in Jubal Early's raid on Washington, DC, the final Confederate incursion into loyal territory.
During the Siege of Petersburg, Breckinridge was made Secretary of War for the Confederate government. When the Army of the Potomac entered Richmond in 1865, Breckenridge ensured that the archives of the Confederate government and military were turned over to the Federals so that historians would one day benefit from intact primary sources. Breckinridge then escorted CS PresidentJefferson Davis on his flight into the Deep South, encouraging Davis to surrender since the cause was lost and further bloodshed would serve no purpose. The two eventually became separated during their travels through the chaotic countryside.
In 1865 Breckinridge began four years of self-imposed exile out of fear that he would be tried for treason, a capital offense. In 1869 he returned to the US after having been granted amnesty. He resumed the practice of law and also began a career as a railroad executive. He mostly retired from politics but did attempt to discourage Confederate veterans from joining the Ku Klux Klan. He died of cirrhosis of the liver on May 17, 1875.