It portrays the powerful scene of the Last Judgement, where the 'dammed and just' are judged in front of Jesus, then descend to hell or climb to heaven. According to Blake's own analysis of the tumultuous action, the figures on the right are wicked and chained to each other, while falling to their fate in the fiery depths of hell. The figures on the left are righteous, and are ascending towards the skies with their families and children. Notwithstanding, for Blake, these figures were intended to represent mental states rather than people. He regarded Jesus as the divine inspiration.

The Countess of Egremont, Elizabeth Ilive (c.1769–1822), commissioned this image. In 1810, she married the 3rd Earl of Egremont, George O'Brien Wyndham (1751–1837), having borne several of his children previously. Nonetheless, their marriage ended a couple of years later, purportedly due to the earl's extramarital activities. The topic of this artwork might have been regarded as especially pertinent, enabling Elizabeth to concentrate on her faith instead of her feelings of regret.

Jesus is depicted near the top of the painting on the Judgement Throne, with paradise opened up throughout the artwork. The heads of children are shown behind Jesus, to signify creation emanating from Christ. Surrounding Jesus are seven angels (holding vials filled with the wrath of God) and the four Zoas. Above Jesus, a tabernacle is displayed that has a cross inside it. To the left of Jesus is the Last Supper, and to the right a baptism image can be seen. Both of these symbols represent ever-lasting life.

The resurrection of the righteous is shown further to right of Jesus, and to his left is the resurrection - then subsequent descent of - the dammed. Moses and Abraham are near to Jesus, while Adam and Eve are just below him. Satan can be seen below Moses, with the Serpent wrapped around him, and the book of death is in the middle. The book of life is at the top and the female figure on the moon represents the Christian Church. Some have speculated that the shape of the painting looks like a human skull. The abundant nude figures could be thoughts falling and rising, with truth and imagination welcomed and negative beliefs rejected. Therefore, the Last Judgment might be a flash of enlightenment.