After working in Canadian and American television, Campbell emerged as a scream queen for her starring roles in horror and thriller films.

She subsequently relocated to the United States to star as Julia Salinger in the Fox teen drama series Party of Five (1994–2000), which became her breakthrough role.

At age six, she saw a performance of The Nutcracker and decided she wanted to take ballet classes, enrolling at the Erinvale School of Dance.

She later moved into residence at the National Ballet School of Canada, training there and appearing in performances of The Nutcracker and Sleeping Beauty.

[16][17] With a desire to perform in Hollywood,[18] Campbell went to Los Angeles to find a talent manager to represent her and ended up going on several auditions while she was doing so.

[27][28] Her work in The Craft was noticed by director Wes Craven, who specifically asked her to audition for the role of Sidney Prescott in 1996's Scream,[29] believing that the actress could be "innocent", but also handle herself once emotional and psychical conflicts arose.

[32] Variety magazine described Campbell as "charismatic",[33] and the Los Angeles Times called both her acting and the character "iconic".

In 1998, Campbell had roles in Hairshirt and 54 and voiced Kiara in the Disney animated musical film The Lion King II: Simba's Pride.

[40] In 2022, a retrospective review of Wild Things in The New York Times written by Abbey Bender described her character as a "femme fatale" and called Campbell's acting a "calculated performance of self-assured femininity inspires fear, arousal and awe in equal measure".

Roger Ebert wrote that she "takes a tricky role and enriches it, brings it human dimension instead of being content with the "sexpot" assignment.

"[42] Campbell starred again as Sidney Prescott in Scream 3 (2000), which earned over $160 million but marked a temporary end for the franchise following mixed reviews.

[49] The following year, she led the independent film When Will I Be Loved (2004), which was praised by critics;[50][51] Roger Ebert wrote that Campbell gave a performance that was "carnal, verbally facile, physically uninhibited and charged with intelligence.

[53] The latter half of the 2000s saw sporadic work from Campbell, due to a hiatus; most notably, in June 2009, she had a starring role on NBC's short-lived series The Philanthropist.

She also appeared in the 2012 miniseries Titanic: Blood and Steel, and starred in the 2013 Lifetime crime film An Amish Murder.

[70][71] On June 30, 2015,[72] it was announced that Campbell would star as Texas-based political consultant LeAnn Harvey in the Netflix television drama House of Cards, beginning in the fourth season.

"[75] Campbell was particularly praised by GQ magazine for her performance, who called her the "best thing" of the season and wrote that "she was exactly the competitor that the show's anti-heroes needed".

[76] In 2016, Campbell was honoured with the National Award of Excellence by the Association of Canadian Radio and Television Artists (ACTRA).

[85] In 2019, Campbell starred as Rebecca Fine, a single mother struggling with a serious illness, in the Canadian drama film Castle in the Ground.

[93] IndieWire stated that she does "a fine job of balancing unimaginable pain with hard-fought moments of joy" and that she "distills Laura Sobiech's religious fervor into a more general desperation".

[94] In September 2020, it was confirmed that Campbell would reprise her role as Sidney Prescott for the fifth Scream film, directed by Matt Bettinelli-Olpin and Tyler Gillett.

[108] The Hollywood Reporter wrote that "... it's a pleasure to see Campbell again in fine form as Sidney, striding back into Woodsboro to take care of unfinished business".

[109] Elle magazine named her the "Reigning Queen of Scream" and stated that "Sidney might not have that impact on people were it not for Campbell's portrayal, rife with vulnerability, intelligence, and a palatable dose of humor.

[123] Campbell expanded on her statement a few weeks later, saying she could not bear "walking on set and feeling undervalued" and that the offer would have been different had she been a man.

[124][125][126] In May 2022, Campbell was cast as Raven in a recurring role for the Peacock television series adaptation of Twisted Metal.

[129] In August 2022, it was announced that Campbell had been cast in the lead role of the ABC series Avalon as Detective Nicole "Nic" Searcy.

[133][134] Swan Song was selected to premiere in the Special Presentations line-up of the Toronto International Film Festival[135] and is scheduled to have a 2024 theatrical release.

[140] In 2020, she and several other Scream co-stars hosted a charity event to raise funds for the National Breast Cancer Foundation.

[76] The role of Sidney Prescott as played by Campbell established her as one of the highest-grossing and acclaimed heroines of all time in the slasher genre.

[160] She was referenced in the single "Here We Go... Again" featuring Tyler, the Creator in the lyric "I loved her right, make her scream like Neve Campbell.

"[161][162] Campbell trended on Twitter in January 2023 when Paramount Pictures was widely criticized for the Scream VI pay dispute.