Samson Agonistes is the tragedy of Samson, a once-mighty warrior brought low by his own pride and lust. The central theme is redemptive suffering. Samson is disempowered, enslaved, and blinded, but ironically, his spiritual sense has never been more keen. His inner strength has increased, as he is able to resist the temptations provided by his faithless wife Dalila and his father Manoa, who both want to take care of him. But instead of running from his pain, Samson embraces and learns from it.

Another theme is freedom. Samson is a prisoner both physically and spiritually. Though he is offered ways out of his physical bondage as a slave, he does not want to devolve into childlike dependency, which would only be another form of imprisonment. So at the play's tragic conclusion, Samson kills both himself and many Philistines, essentially taking back control of his person and lashing back at his enemies.

The relationship between God and man is another important theme explored by Milton in Samson Agonistes. Samson believes that he's been punished by the Almighty for his sins and for not keeping his vows. As he sits languishing inside a Philistine prison, he broods over his fate, blaming himself for his hopeless predicament.

With Samson, there is no sense that God is a personal, loving deity, but rather a cruel tyrant, a cloud-dwelling law-giver who regularly dispenses the very harshest of divine justice to those who sin against him. Milton presents the relationship between God and man as characterized by what the Danish philosopher Kierkegaard called an "infinite qualitative difference." Man is man, and God is God, and there's simply no bridge between them except through the mediation of Christ. But as Samson lives in the pre-Christian era, he's completely separated from God and so remains an object of divine wrath rather than loving forgiveness.