The season premiere kicks off with the FBI hunting Liz for the murder of the Attorney General. Red and Liz are named to the FBI's Ten Most Wanted Fugitives list and set out on the run to evade capture. Red calls upon a Blacklister called "The Troll Farmer," to help them flee the city, while the task force must question whom of their own can still be trusted. Dembe is put in a dangerous and compromising position.

Red and Liz take a detour towards the Midwest as part of their mission to exonerate Liz and defeat the Cabal. Ressler, Samar and Aram continue to track the fugitives and in the process stumble upon what could become a global food crisis. Meanwhile, Cooper turns to an unlikely ally.