Premiering at the Theatre Royal, Drury Lane the original cast featured Barton Booth as Cato, Theophilus Keene as Lucius, John Mills as Sempronius, Robert Wilks as Juba, Colley Cibber as Syphax, George Powell as Portius, Lacy Ryan as Marcus, John Bowman as Decius, Anne Oldfield as Marcia and Mary Porter as Lucia.

Frederick, Prince of Wales put on a production at Leicester House on 4 January 1749 to promote his own support for English liberty against the supposed tyranny of his father, George II of Great Britain.

George Washington, for example, attended a performance of Cato with his officers while encamped at Valley Forge with the Continental Army in 1778.

In Cato's court are his twin sons Marcus and Portius, his daughter Marcia, the exiled Numidian prince Juba (an ally of Cato whose father, Scipio, Caesar killed in the battle of Thapsus), Juba's servant Syphax, and the senior senators Sempronius and Lucius.

Juba finds Marcia cavorting with her friend Lucia and flirts with her, but she scolds him for being distracted by romantic fantasies during a dire crisis.

Lucia chides Marcia for spurning the advances of the rich and handsome prince and confesses that she herself is in love with Portius and that they are eloping.

Marcia sympathizes with her but warns her that Marcus loves her as well, and his jealousy will drive the brothers apart forever if he finds out about Lucia and Portius' relationship.

In the Senate, Sempronius grows tired of waiting for Syphax to turn Juba's allegiances, and raises his own mutinous legion to overthrow Cato.

Sempronius realizes Cato cannot be deposed by troops so loyal to him and resolves to abandon his plot, abscond with Marcia, and leave Utica to join Caesar's legions.

However an anguished Marcus, no longer concerned whether he lives or dies, viciously attacks them to defend his father and slays Syphax before being slain himself.

With his dying breaths, Cato gives Marcia his blessing to marry Juba, who he declares is a Numidian with "a Roman soul."

He declares that the tragic story of Caesar's conquest will stand forever in history as a warning to all nations of the dire cost of civil war.

Some scholars, including historian David McCullough, the author of 1776, believe that several famous quotations from the American Revolution came from or were inspired by Cato.

Thomson wrote, “I am ready to ask with the poet [referring to Joseph Addison] 'Are there not some chosen thunders in the stores of heaven armed with uncommon wrath to blast those Men, who by their cursed schemes of policy are dragging friends and brothers into the horrors of civil War and involving their country in ruin?'

For example, John Trenchard and Thomas Gordon were inspired by the play to write a series of essays on individual rights, using the name "Cato."

Wilkins Micawber, a character in the 1850 novel David Copperfield by Charles Dickens, quotes Cato from the play: "Plato, thou reasonest well."

Anderson's young adult novel The Astonishing Life of Octavian Nothing, the main character also quotes the play, "A day, an hour, of virtuous liberty/Is worth a whole eternity in bondage" (p. 346).