She is played by Kristin Kreuk.
Born in in the 17th century in the French village of Castelnau-de-Montmiral, Isobel was a French aristocrat and witch, as well as Lana Lang's maternal ancestor. She was enlisted by Duchess Gertrude, also a witch as well as the ancestor of Genevieve Teague and Jason Teague, to help her find the Stones of Power, three Kryptonian artifacts that would create the Fortress of Solitude. While visiting a mystic, she saw a Kryptonian in a globe. The Kryptonian told Isobel that they could rule together if she gathered the stones, so she left the mystic's tent with the idea that she could someday rule Earth. Her power-lust led her to betray Gertrude, stealing her map which led to the Crystal of Air.
Aided by Brianna Withridge and Madelyn Hibbins, Isobel searched for the Stones of Power, only for Gertrude to accuse the trio of witchcraft, leading to their capture by the townspeople. Before she was burned at the stake along with her partners in crime, Isobel spat blood on her book of spells, and the blood mixed with the symbol on the book. As she burned, Isobel vowed that her heir would awaken her and that she would gain the stones as well as vengeance.
Centuries later, in 2004, Lana Lang did a rubbing of Isobel's tomb in a Paris church when she was exposed to a blast of light that left her branded with Isobel's mark. Later, in the episode "Spell," Lana bought Isobel's spell book on eBay. After Lana touched the book, Isobel possessed her body. She then made a potion that allowed the spirits of Madelyn and Brianna to possess Chloe Sullivan and Lois Lane, respectively, and also stole a Russian manuscript containing Gertrude's map from Lex Luthor, enchanting Lex to play the piano forever.
Isobel and her henchwomen crashed Chloe's birthday party at the Kent Farm, where they cast a spell causing everyone, including Clark Kent, to lose their inhibitions and act wildly. Clark later figured out what was going on and confronted Isobel just as she reclaimed her spell book from Jason, but Isobel escaped, leaving Clark a message to meet her in his barn at midnight. After arriving in the barn, Clark battled the witches, who gained the advantage in the fight by magically stripping him of his powers. Isobel then magically extracted the location of one of the stones from Clark before leaving with her comrades. The witches entered the Kawatche Caves, where they opened a hidden chamber. When Clark arrived, armed with a shotgun, Isobel touched the Crystal of Fire, only for it to burn, causing her to drop it. When Clark grabbed the crystal and it restored his powers, Isobel threatened to take them away again, but Clark, acting quickly, used heat vision to destroy her spell book, restoring Lana, Chloe, and Lois to their normal selves.
In "Sacred," when Lana was being tortured by Chinese officers, Isobel possessed her a second time, and she got free from the officers before revealing that Gertrude's map led to one of the stones. After knocking Clark out, she went to the stone's location and unearthed a statue, which she broke to reveal the Crystal of Air. When Clark showed up to claim the crystal, Isobel engaged him in a fight using enchanted Chinese swords. Clark got the Crystal of Air away from Isobel, but when they both touched it, an explosion occurred, seemingly ending Isobel's control over Lana once again.
In "Commencement," when Lana was being strangled by Genevieve, Isobel possessed her descendant for the final time to overpower Genevieve. She then used the Crystal of Air to stab Genevieve in the heart, killing her. Having finally exacted her long-sought revenge, Isobel left Lana's body for good.