2015–2019: Breakthrough
Johnson's breakthrough came with her leading role as Anastasia "Ana" Steele in the erotic romantic drama film Fifty Shades of Grey, which was released in February 2015 and brought her international recognition. Johnson won the role over Lucy Hale, Felicity Jones, Elizabeth Olsen, Danielle Panabaker, and Shailene Woodley. In response to questions regarding her stance on gender rights concerning her character in the Fifty Shades film series, Johnson stated: "I'm proud of [the film]. I completely disagree with people who think Ana's weak. I think she's actually stronger than he is. Everything she does is her choice. And if I can be an advocate for women to do what they want to do with their bodies and not be ashamed of what they want, then I'm all for that." While the trilogy was widely criticized, Johnson received praise for often being the standout performer. However, her role in the first film won her first Golden Raspberry Award for Worst Actress, as well as an Award for Worst Screen Combo, which she shared alongside Jamie Dornan. She received nominations in the same categories for Fifty Shades Darker (2017), though she did not win. She reprised her role for the trilogy's final film, Fifty Shades Freed (2018).
On February 15, 2015, Johnson appeared on Saturday Night Live's 40th anniversary special and hosted SNL on February 28, 2015, making her the second daughter of a former SNL host (after Gwyneth Paltrow, whose mother Blythe Danner hosted during the show's seventh season in 1982) to host the show. Also in 2015, she reunited with her 21 Jump Street cast member Johnny Depp, playing the mother of his character's child in the feature film Black Mass. Jessica Kiang of IndieWire said that she "makes something of nothing" in her role. In 2015, Johnson starred in Luca Guadagnino's thriller A Bigger Splash, alongside Tilda Swinton, Matthias Schoenaerts, and Ralph Fiennes. Writing for Rolling Stone, Peter Travers stated that Johnson showed that her character "has more on her mind than slithering seductively". According to Christy Lemire from RogerEbert.com: "A Bigger Splash allows Johnson to be both funnier and sexier than she was in Fifty Shades of Grey". The same year saw the release of Cymbeline, a modern film adaptation of the William Shakespeare play, in which she starred alongside Ethan Hawke and Ed Harris. She also played a lead in the 2016 comedy How to Be Single, with Leslie Mann and her Date and Switch co-star Nicholas Braun. She performed a cover of the Frankie Valli song "Can't Take My Eyes Off of You", alongside Zani Jones Mbayise, Vanessa Rubio and Damon Wayans Jr. for the soundtrack of the film. Johnson was invited to join the Academy of Motion Picture Arts and Sciences in June 2016.
Johnson starred in Luca Guadagnino's supernatural horror film Suspiria (2018), a remake of the 1977 film, in which she played an American dancer in Berlin who enrolls in an academy run by a coven of witches. David Ehrlich of IndieWire described Johnson's performance in the film as "thrillingly unrepentant". Also in 2018, she starred in Drew Goddard's neo-noir thriller Bad Times at the El Royale, with Jeff Bridges, Jon Hamm, Cynthia Erivo, and Chris Hemsworth. In the film, she played a hippie staying at a resort on the California-Nevada border where the lives of various people with suspicious pasts intersect. Screen Rant ranked Johnson's performance as the fourth-best in the film and stated that "she brings a reserved, under-the-surface power to her role".
In 2019, Johnson starred opposite Armie Hammer in Babak Anvari's psychological horror film Wounds, which is based on Nathan Ballingrud's horror novella The Visible Filth. It had its world premiere at the Sundance Film Festival on January 26, 2019. Johnson starred in the well-reviewed independent adventure film The Peanut Butter Falcon, alongside Shia LaBeouf, Zack Gottsagen, and Bruce Dern. The film premiered at South by Southwest on March 9, 2019. It became the highest grossing independent film of the year. While promoting the film on The Ellen DeGeneres Show, Johnson had a notably tense interaction with the show's host Ellen DeGeneres regarding a birthday party invite – leading to Johnson saying the now-famous phrase, "that's not the truth, Ellen." She starred in Gabriela Cowperthwaite's drama film Our Friend, alongside Casey Affleck and Jason Segel. The film is based upon real life couple Nicole and Matthew Teague, faced with Nicole's impending death, see their best friend move in with them to help them out. Johnson sang again during the film, performing a cover of "If I Had the World to Give" by the Grateful Dead. Joe Morgenstern of The Wall Street Journal wrote that the "intimacy of Ms. Johnson's performance is extraordinary. She is the least assertive of movie stars, yet the courage, despair and fury she finds in Nicole will lift you up and spin you around". While Gary Goldstein from the Los Angeles Times stated that Johnson "impresses with affecting range — from flirty, ebullient and adoring to stalwart, enraged and resigned; it's a lovely performance".