Gargamel the sorcerer is the sworn enemy of the Smurfs. He is an evil wizard, though his powers appear very limited; he actually seems to be more of an alchemist as his main ability is to create magic potions. His main goal in life is to destroy the Smurfs. He is perpetually stooped, his robe is worn and patched, and his teeth are rotten.

He lives in a run-down hovel with his flea-bitten cat Azrael (named after the biblical angel of death). In later episodes he acquired an apprentice named Scruple, who was frequently rejected from a boarding school for young wizards and only Gargamel was willing to teach him magic. Scruple seems moderately brighter and more savvy than his master, though still inexperienced in the ways of magic. Although Scruple aids Gargamel in capturing the Smurfs, his main problem is with the students of the wizard academy who berate him for failing to qualify for admission. The smugness of the students however, proves to be a weakness for them, as Scruple has some success using Gargamel's magic to cause them problems.

When Gargamel first appeared in The Smurfnapper (published in 1959) he captured a smurf which he needed as an ingredient for a potion to make gold (according to an old magic spell). The other smurfs rallied against him, freed the kidnapped smurf and the sorcerer was defeated and humiliated. Gargamel swore revenge: from now on the conflict would be personal.

Sometimes he wants to eat the Smurfs, other times he wants to use them to make gold, and still other times he has even more bizarre uses for them (in one instance he is so enraged by his loss that he yells "I don't want to eat them, I don't want to turn them into gold, all I want now is to DESTROY THEM!"). Though he often catches Smurfs who wander by his home or which he happens across in the forest, he does not know the location of the hidden Smurf village, a fact which continually frustrates him.

On some occasions, he has discovered the location of the village, but sooner or later gets led away from it due to either a magic spell put on him by Papa Smurf or because of some other bizarre factor. Sometimes it is simply a matter of his being led away from the village while chasing the Smurfs, losing them and then being unable to find his way back.

Gargamel has also worked with other enemies of the Smurfs, although in many cases these other villains, such as Count Baltazar, prove to be much more efficient and focused enemies of the Smurfs, and even so much as smash their alliance with Gargamel and enslave him. Not much is said of Gargamel's relationships with women, although in one episode an ugly witch named Hogatha turns herself into an attractive woman in order to seduce Gargamel into giving him secrets, to which she almost succeeds except her constant transformations from ugly to beautiful prove to be too hard for her, and Gargamel eventually is informed of the ruse.

Gargamel is an eternal bungler. Some of his schemes to catch Smurfs border on the bizarre (such as a "blue magnet" that attracted solely blue items). He has a seemingly endless library of spellbooks, potions, and gimmicks for his life's passion. However, no matter how elaborate Gargamel's plans, they invariably end in failure, causing him to spout his catch phrase: "I hate those Smurfs!". (It is worth noting that he does love at least one Smurf, his daughter/creation Sassette who refers to him as "pappy Gargamel.")

Unlike many cartoon villains who always fail, Gargamel was one of the few to actually succeed in his dastardly plans. In one episode he actually succeeds at abducting some Smurfs and transforming them into gold. His success his short lived, when his gold is stolen by highwaymen. The highwaymen are eventually arrested for the theft, but the prince of the kingdom also orders Gargamel's arrest when it is learned he minted the gold without a license from the prince. Papa Smurf is then able to revert the Smurfs to normal.

Despite his never-ending hatred and frustration for the Smurfs, more than once has he had to rely on Papa Smurf to help save him from a more wicked enemy's plans (such as Balthazar) or to rescue him from a potion gone horribly wrong. On another occasion, the episode "The Fountain of Smurf", Papa Smurf drinks too much water from the fountain and becomes a smurfling. The Smurfs rely on Gargamel to come to their aid and help turn Papa Smurf back. In quite a funny, and ironic, ending, Gargamel and Azrael, themselves, fall into the Fountain of Youth.

In 1989, the final season of the series, where the Smurfs are constantly traveling through time, different incarnations of Gargamel would appear, such as showing him as a Indian fakir, a Russian peasant, or a Spanish bullfighter. In one of the earlier episodes of the final seasons, where Gargamel is shown as an Egyptian pharaoh, Papa Smurf believes that all these similar-looking men (and their cats) seen must be ancestors of the infamous Gargamel and Azreal of their present time.

In the original series, Gargamel was voiced by the late Paul Winchell, and Azrael's voice was provided by the late Don Messick.