The story begins when the lawyer Gabriel John Utterson hears from his cousin Richard Enfield of an ambiguous, solitary, violent man called Hyde. This Hyde is said to have "trampled" over a girl whom he met on the road, leaving her bruised and terrified.

Hearing this tale, Utterson is perturbed; a friend of his has made a will declaring that in the event of the doctor's death or disappearance, Hyde should inherit all his property. Suspecting trouble, Utterson starts to investigate Hyde.

This investigation begins as a matter of curiosity and concern despite Dr Jekyll's assurances that Hyde is nothing to worry about. That changes when Hyde is seen murdering a respected Member of Parliament. As Utterson assists in the investigation of the crime, Jekyll becomes more and more reclusive and sombre. This leads Utterson to believe that Hyde has some influence over Jekyll, which he is using to conceal himself.

Eventually, Jekyll isolates himself in his laboratory gripped with an emotional burden that no one can comprehend. Another friend of Utterson's, Dr. Hastie Lanyon, suddenly dies of a horrific emotional shock with which Jekyll seems to be connected. Eventually, Jekyll's butler comes to Utterson to ask for his help to deal with a stranger who has somehow entered the locked lab and killed Jekyll. Together they discover that the stranger in the lab is Hyde, and they break in only to find Hyde dead and Jekyll nowhere to be found.

Eventually, Utterson reads three letters left for him from his deceased friends. The first one is a will made out to his name. The second is from Lanyon and reveals that he witnessed firsthand that Hyde is none other than Jekyll physically transformed into the other identity by means of a potion of Jekyll's design.

This time, Hyde does not just indulge himself; he commits murder, and can no longer be seen in public for fear of being recognised and sent to the gallows. This reassures Jekyll, and he attempts to redeem himself for the actions of Hyde by being charitable. However he once more undergoes the transformation, without the aid of his potion, in a park in broad daylight. He manages to avoid capture by finding a hotel room. He writes to Lanyon, asking him to fetch from his study the drawer in which the counter-agent is found.

Lanyon complies, and Hyde shows up at his house unrecognised. He takes the potion, as although he has begun to despise Jekyll, he fears recognition and the resulting death even more. He changes into Jekyll before Lanyon's astonished eyes. Heartbroken by this shocking revelation, Lanyon wastes away and dies.

Jekyll finds that he can now only remain in his original form with the potion in his system. Eventually Jekyll ran out of the unique components to the potion, and in particular a "salt" of which he had initially acquired quite a large quantity. New supplies of this salt did not produce an effective potion, which he initially attributed to an impurity in the new supplies, but finally concluded that it was the initial order that was impure, and that an "unknown impurity" in it was vital to its effectiveness. As he had no way of acquiring any more of this impure salt, he was doomed to remain as Hyde permanently.

In the end, Jekyll decided to write the confession letter, and he finally "dies" as he transforms completely into Hyde. Hyde commits suicide, when Utterson and Jekyll's butler try to force their way into the laboratory.

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