MacLaren made her directorial debut on the season nine episode of The X-Files, "John Doe", which was written by her future Breaking Bad collaborator Vince Gilligan. She was nominated for six Primetime Emmy Awards all for Breaking Bad: one for directing the episode "One Minute" (season 3, episode 7) in 2010, one for directing the episode "Gliding Over All" (season 5, episode 8) in 2013, and the other four in 2010, 2012, 2013 and 2014 for Outstanding Drama Series, on which she served as an executive producer, winning in 2013 and 2014. She was also nominated for three Producers Guild of America Award for Best Episodic Drama for Breaking Bad, winning in 2014 and 2015. In June 2014, it was announced MacLaren had signed a two-year first-look deal with HBO.

In November 2014, it was announced that MacLaren would develop the script and direct Wonder Woman, the iconic character's first solo cinematic appearance and the fourth installment of the DC Extended Universe. However, in April 2015 MacLaren left the project due to "creative differences". She is currently set to executive produce and direct the pilot for David Simon's HBO drama The Deuce. In August 2016, it was announced that MacLaren would be directing the film adaptation of Kristin Hannah's novel The Nightingale. The same year she also directed the ninth episode of the HBO series Westworld.

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