The First Blade was a weapon capable of killing any known being.

Originally thought of as God's favorite, Abel believed he was getting direct messages from God but he was, in fact, talking to Lucifer. In an effort to protect his brother from corruption, Cain offered himself to Lucifer so that Abel would go to Heaven instead. Lucifer agreed, on the condition that Cain himself would send his brother to Heaven. Cain then fashioned a weapon out of the jawbone of a donkey and used it to kill his brother.

God had created a Mark which served as the seal created in order to lock away The Darkness and put it in Lucifer. Lucifer transferred the mark to Cain, which somehow linked its power with the blade. This made the First Blade, when held by the bearer of the mark, powerful enough to kill anything. However, without the mark, the blade would simply be a bone.

Cain later copied the Mark onto Dean Winchester, so that the hunter could kill Abaddon. It was removed from its final bearer when Rowena cast a spell from the Book of the Damned, but unknowingly released The Darkness upon the Earth. When the Darkness took human form, the Mark was transferred to her permanently, thus rendering the Blade useless and powerless.