He went to several auditions. After meeting a manager he got one of the main roles in MTV's "Teen Wolf", a series based on the 1985 movie of the same name. He was originally planning to audition for the role of Scott, but after reading the script, O'Brien decided to audition for the role of Stiles. In 2013, O'Brien co-starred in the comedy movie "The Internship", with Vince Vaughn and Owen Wilson. O'Brien played the lead role as Thomas in "The Maze Runner", a movie adaptation of the novel of the same name. They began filming in the summer of 2013. At the end of October 2014, he started filming the sequel "" in New Mexico. It was released on September 18, 2015 in the United States.