Season two has several changes to Don's FBI team: Terry Lake is reassigned to Washington and two new members join Don and David Sinclair: Megan Reeves and Colby Granger. Charlie is challenged on one of his long-standing mathematical workpieces and starts work on a new theory, cognitive emergence theory.

Charlie and Amita intensify their relationship, as do Larry and Megan, especially after Megan's kidnapping. Amita has trouble adjusting to her new role as a CalSci professor, and Larry announces his leave of absence; he will be on the International Space Station for six months, which greatly distresses Charlie.