The play is loosely modeled on historical events in the 16th century under the reign of King Philip II of Spain, following the title character of Don Carlos.

It deals with both Prince Carlos' personal emotional and political struggles, the latter of which are made clear through the figure of the Marquis of Posa, who fights for liberty during the rule of Catholic Spain during the Reformation.

The Marquis has returned from long travels as a spokesperson for the Netherlands, who are largely protestant and struggling against Spain's catholic occupation, and hopes to gain Carlos' support.

Carlos talks to King Philip and asks for both reconciliation and to be sent to Flanders to deal with the insurrection, like Posa urged him to, despite his lingering resentment against his father.

As King Philip hears about the meeting between Carlos and the queen as well as several rumours, mostly from Alba and Domingo, he grows more and more paranoid and distrustful of his wife and son, ready to kill them.

Posa initially refuses to serve the king and holds a moving speech for humanity, pleading to free the peoples' minds rather than continuing an oppressive rule.

Philip, impressed by his courage and outspokenness, makes him a minister and personal advisor; further, he now sees him as a friend who can uncover the true relationship of Carlos and the queen.

In 1982, Lesley Sharpe argued that with Don Carlos, Schiller moved away from character-based drama, and that the play's universe "casts a shadow of ambiguity" on its characters because of the complexity of the situation.

[2] Gorner argued that the "sheer musicality of Schiller's verse" is shown by such works as Don Carlos, as well as The Robbers (1781) and Intrigue and Love (1784).