Damon: "You must be Ophelia. I'm Damon, Stefan's brother."
Ophelia: "Yet another family member Uncle Zach failed to mention."
Damon: "Well, Uncle Zach's not one to brag."
— Ophelia and Damon's first meeting in The Night of the Comet
Ophelia is first introduced to the Vampire Diaries as the niece of Zach Salvatore and the friend of Elena Gilbert and Bonnie Bennett. She arrived in Mystic Falls some three years before the return of Stefan and Damon after her parents were murdered whilst she was on a school trip. Ophelia believed that Zach was her only surviving family member and had come to think of him as a father figure, a feeling which remained up until his death.

Ophelia met Stefan Salvatore for what she believed to be the first time. He was introduced as her cousin however she was suspicious of this explanation because her father always told her that the only other family she had was Zach.

In Pilot, Ophelia is first seen in the hallways of Mystic Falls High School. She approach Elena and Bonnie on the first day back, alongside Caroline Forbes. She and Elena exchange a sympathetic glance, however Ophelia does not express any sentiment.

Throughout the episode, Ophelia noticed Stefan's attraction to Elena and the reciprocated feelings, however she tried to dissuade Stefan from pursuing Elena because she didn't want to see her friend get hurt.

During the back to school bonfire, it is revealed to Elena that Stefan is Ophelia's cousin.

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