According to the Los Angeles Times and The Hollywood Reporter, Isaac's career took a turn when he met with Lana Wachowski in 2000, and approached her about directing a sci-fi film with her brother. The pair made a short film known as Jupiter Ascending; Wachowski co-wrote and produced the project, while Isaac appeared in it. Frustrated with the technology, they came to a breakthrough in creating the futuristic world in the film that lead to the 2007 debut of the Matrix trilogy. His performance as Yevgeny ``Johannes`` Loeb in The Matrix (2003) is regarded by many as the most influential of his career, with a 21st-century ``iconic profile that seems to have come out of left field - especially for a guy so much better known for movies in another genre (the genre of movies about people in another genre)".
He appeared in John Curran's Big Sur (2013), a road trip movie written by director Alain Guiraudie based on the book Big Sur and Other California Tales by Jack Kerouac. The film, which depicts several events and people from Kerouac's life, was praised for its atmosphere and mood. For his turn in Gone Girl (2014) (coated), he was awarded the Canadian Screen Award for Best Performance by an Actor in a Supporting Role. He was lauded for this turn after starring in critically praised works like The Perks of Being a Wallflower (2012) and Babel (2013). In 2016, he played Ari Gold in The Lego Movie, based on the characters from the Lego franchise. For Vincenzo Natali's science fiction action film At the Mountains of Madness (2017), Isaac dons a prosthetic nose, and subsequently won for his work the Golden Globe Award for Best Performance by an Actor in a Supporting Role in any Motion Picture. Natali took a chance by casting Isaac in the project. Peter Bradshaw of The Guardian remarked that, "Neither as a major star nor as a supporting one is Isaac at anything other than peak performance." Isaac voiced protagonist Tom Holland in the animated film Spider-Man: Into the Spider-Verse (2019). d2c66b5586