The First Blade was the only weapon that could kill Knights of Hell.
When Cain realized that his brother Abel was talking to Lucifer, and not God, Cain offered an exchange where his younger brother would go to Heaven and Cain would take his place in Hell. Lucifer agreed, on the condition that Cain himself would send his brother to Heaven. Cain then fashioned a weapon out of the jawbone of an animal and used it to kill his brother.
Lucifer gave Cain a mark, which acted as the blade's source of power. This made the First Blade powerful enough to kill Knights of Hell. However, without the mark, the blade would simply be a bone.
1863EditCain has since retired from his job, having met his wife Colette, who forgave him despite his deeds. However, this angered the Knights of Hell, leading Cain to destroy his very creations. In Jasper Springs, Mississipi, he hunted demons protecting the last remaining knight. To his shock, he found out that Abaddon had possessed Colette. Abaddon threatened to kill Colette if Cain did not return to his job as a knight. Cain refused and stabbed his wife with the First Blade, but not before Abaddon left Colette's body.
At this time, Cain made a promise to Colette that he would no longer work as a Knight. Since nothing could destroy the First Blade, Cain threw it into the bottom of the deepest ocean during his retirement, so that he would be able to keep his promise.
The First Blade was being located by Crowley in order to give it to its new owner, Dean, who also has been given the Mark of Cain. The two want it to kill Abaddon as it is the only weapon that can kill a Knight of Hell.