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Melonie Diaz as Mel Vera, the middle half-sister in the family. A "strong-willed feminist" and "passionate, outspoken activist," Mel is a graduate student in the women's studies department at Hilltowne University. She is a lesbian who was previously in a relationship with Niko (Ellen Tamaki) and Jada Shields (Aleyse Shannon). A "time witch," Mel was born with the power of time-freezing, similar to the original middle sister Piper Halliwell (Holly Marie Combs) from the original series, and later develops the power to send people and objects through time. She also develops molecular manipulation, even more similar to Piper's powers, which allows her to slow or accelerate molecules to make ice, or to heat up and explode objects.
Madeleine Mantock as Macy Vaughn (seasons 1–3), the eldest sister. She is a "practical", "driven", "shy" and "intense science nerd". Macy has a PhD in molecular genetics and initially moved to Hilltowne, Michigan, to work in the university lab. Once she arrives in town, Macy discovers that she has a younger half-sister and a younger sister. Macy has the power of telekinesis, similar to the original eldest sister Prue Halliwell (Shannen Doherty) of the original Charmed series. Macy was stillborn as a baby but was brought back to life by necromancy, which caused her to have a demon side. She is later stripped of her demon aspect in the second season. She and her Whitelighter Harry become a couple at the end of the second season. In the third-season finale, she dies in a similar fashion to her counterpart Prue.
Sarah Jeffery as Maggie Vera, the youngest sister. She is a "bubbly", "fun-loving" and "kindhearted" freshman at Hilltowne University who is pledging a sorority. Maggie is initially mortified to learn that she is a witch as she wants to be well-liked and fit in. Maggie has the power of empathy, the ability to read the emotions of other people, which expanded to being able to hear thoughts too. This is one of the first differences from the original show as the original youngest sister Phoebe Halliwell (Alyssa Milano) from the original series initially had the power of premonition, before developing empathy in the later seasons. Later, Maggie develops similar powers to Phoebe in the original Charmed, including the power of foresight, the ability to transfer her emotional state to others, and eventually the ability to empathically mimic the powers of people she touches.
Ser'Darius Blain as Galvin Burdette (season 1), a molecular geneticist who works at the Hilltowne University lab with Macy Vaughn. He is "outgoing" and "generous", and is the first person who befriends Macy when she moves to Hilltowne. He enters into a relationship with Macy but ultimately sacrifices himself at the end of the first season to stop the Harbinger virus.
Ellen Tamaki as Niko Hamada (season 1), a "smart" and "determined" detective with the Hilltowne police department. She dates Mel Vera until Mel uses a spell to reverse time so that they never met in order to protect her. Niko returned to Hilltowne as a private investigator and encountered Mel. It is revealed that Niko had a mental breakdown which led to her changing careers, she is engaged to marry Greta, the woman she was with before she met Mel in the original timeline, but her interactions with Mel cause trouble between them much like the original timeline, especially after she learns about Mel's status as a witch and their past relationship. By the end of the first season, Mel decides to let Niko go and move on.
Rupert Evans as Harry Greenwood, the sisters' Whitelighter – a guardian angel who protects and guides witches. In the first episode, Harry initially poses as a professor and the chair of the women's studies department at Hilltowne University until he gathers all three sisters together to reunite them and inform them of their destiny as the Charmed Ones. He does not remember his life as a human. By the end of the first season, he is shown to have developed feelings for Macy. At the end of the second season, he and Macy become a couple. Evans also portrays Harry's Darklighter in the second season.
Nick Hargrove as Parker Caine (season 1; recurring season 2), Maggie Vera's boyfriend. He is the president of the Phi Delta Upsilon fraternity. He and Maggie become friends after he defends her from a rude customer at her waitressing job. He is later revealed to be a half-demon sent by his father to wreak havoc on the sisters. He betrays his father as he falls in love with Maggie but is forced to leave at the end of the first season to deal with his demon side. He later returns during the second season, where it's revealed that he has taken over demonkind as its new Overlord. After his sister usurps his position as the Overlord, he willingly allows Abigael to strip him of his demon side, which renders him mortal.
Jordan Donica as Jordan Chase (seasons 2–4), a law student and amateur boxer. It is later revealed that his family was cursed by a witch due to his ancestor having spearheaded the witch's execution, with the result that the men in his family do not live past the age of 25. He breaks the curse for himself but wants to find a way to break it permanently for the sake of his descendants.
Poppy Drayton as Abigael Jameson-Caine (seasons 2–3), a demon-witch rescued and recruited by Macy. She is later revealed to be a member of the Caine family, being Alistair's daughter and Hunter's and Parker's half-sister, and has a secret agenda to take over demonkind as its Overlord by stealing the position from Parker.
Lucy Barrett as Kaela Danso (season 4), an artist and mechanic from Philadelphia with the magical power of imagination manifestation. After Macy's death in the third season, Kaela is revealed to be the new Charmed One who helps reconstitute the Power of Three, although her ties to Maggie and Mel are left ambiguous at the time of her introduction. It is later revealed that she is linked to the sisters due to having received a stem cell donation from Macy while battling cancer, which also resulted in her powers manifesting.
