As the story begins, the narrator tells us what he knows about Ligeia – or, rather, what he doesn't know. He can't remember when they met, where she came from, her family history – well, aside from something vague about an old city by the river Rhine. He can't even remember her last name.
Still, she's far from forgotten: the narrator starts talking about his passion for Ligeia, which is something he certainly can't forget. He continues on from there, describing the way she carried herself, with such grace. He goes on to tell us about the subtle strangeness of her beauty; her white skin, her raven-black hair, her delicate profile and elegant mouth and brilliant teeth and bright smile. Then he moves on to her unique and heavenly eyes, and further still to her expression, "that something more profound than the well of Democritus" (4). He can't do much to describe her expression, although he's constantly coming up with analogies to it. Always, though, it reminds him of the quote from Joseph Glanvill that opens the tale – "And the will therein lieth."
From there he speaks of the intensity with which she did everything, of the passion that consumed her, and of her great intelligence, unmatched by any other woman – all things that consumed and inspired him, too. Soon, though, he tells us about how Ligeia's intensity began to decrease, how she fell ill, and how her illness devastated him.
He goes on to describe the moments before Ligeia's death: As he sits by her bedside that night, she asks him to repeat a poem that she had written a few days before. It's called "The Conqueror Worm," and it tells the story of a strange play, in which mimes play Man and the conqueror worm triumphs over all. Once the poem has been recited, Ligeia wonders out loud if "the conqueror" might not win this time, repeats the Glanvill quote, and then dies.
After Ligeia dies, the narrator leaves for England, where he moves into an old abbey. Having inherited Ligeia's fortune, he's become quite rich and soon takes a new wife, Lady Rowena Trevanion, of Tremaine. Unfortunately, he doesn't love her; in fact, he hates her. He puts her up in a strange "bridal chamber," decked out with Egyptian sarcophaguses and strange gold curtains that make the whole place one big optical illusion. All the while, our narrator's mind is constantly on Ligeia, and he begins to smoke opium to ease his pain.
At the beginning of the second month of their marriage, Lady Rowena gets sick, and though she briefly returns to health, she eventually falls into a strange funk, and starts to have hallucinations. The narrator passes these off as mere illusions created by the curtains, but one night things really take a turn for the worse.
Seeing that his wife's on the verge of fainting, the narrator brings out some wine to try to revive her – but he's interrupted by a strange sensation. He can feel a sort of invisible figure pass him by and then, soon after, he sees a faint shadow on the carpet. He passes these off as his own hallucinations – he's high on opium, after all – but his visions become more and more potent. Soon he hears footsteps and sees strange red drops of liquid fall into Lady Rowena's glass of wine. When Rowena drinks from the cup, she immediately gets sicker and soon dies.
Now the narrator finds himself sitting at the side of Rowena's shrouded body, but his mind, fogged by opium, is still on Ligeia. Around midnight, he notices something strange – a faint cry coming from Rowena's bed. A few minutes later, he notices that a bit of color has returned to her cheeks; he decides that she's still alive. All alone, he attempts to bring his wife back to life, but to no avail – she soon fades back into death, looking even worse than she did before. He has more visions of Ligeia, visions that are interrupted by a second, more drastic revival. The same cycle occurs again – he fails to bring her back, she falls back into death, looking even worse than before, and he begins to have visions.
Finally, early in the morning, Rowena has an even more dramatic awakening: even though she's still wrapped in her burial shroud, she looks very much alive. He watches her rise from the bed and advance toward him. Yet, he notices that she seems taller than before. When he leaps up, she lets the bandage fall from her head, revealing huge amounts of dark black hair. He knows, then, that he is looking into the eyes of Ligeia.