Five years after the events of the first encounter with extraterrestrial life, Agent J has become a top operative for the secret organization known as MiB, which polices alien activity on Earth. Despite his successful career, Agent J struggles with the high turnover of partners and the absence of his former mentor, Agent K, who has since had his memory wiped and returned to civilian life. When a mysterious alien known as Serleena arrives on Earth in search of a powerful artifact called the Light of Zartha, Agent J discovers that the only person with knowledge about its whereabouts is the retired Agent K.

Realizing the severity of the threat posed by Serleena, Agent J finds and convinces a reluctant Agent K to rejoin MiB and restore his memory. They must race against time to piece together the clues K left behind in his past life before his memory was erased. The agents delve into old cases while being pursued by Serleena, who will stop at nothing to obtain the Light of Zartha and achieve her nefarious goals. The fate of Earth hangs in the balance as the pair battles both time and intergalactic criminals.