Shirō Sanada serves as science officer and later executive officer aboard the space battleship Yamato. A childhood accident claimed his sister's life and resulted in his bionic limbs, fostering resentment toward scientific arrogance. He attended school with Mamoru Kodai and harbors lasting guilt over Mamoru's death, stemming specifically from his failure in the 2199 timeline to inform Mamoru that Operation M was a suicide mission rather than inadequate repairs to the Yukikaze.

Sanada consistently functions as the Yamato's second-in-command across iterations. During the 2199 events, he serves as First Officer under Captain Jūzō Okita, maintaining an analytical and reserved demeanor characterized by tactical competence and emotional restraint. He provides guidance to acting captain Susumu Kodai during command transitions and repeatedly accepts responsibility for operational failures regardless of direct involvement.

By 2205, Sanada commands the carrier ship Hyūga within the Yamato fleet while continuing his strategic advisory role. His scientific expertise proves crucial when analyzing wreckage inside the Dezariam mothership, where he identifies remnants of Andromeda-class warships that should not exist in that time period, suggesting potential enemy time travel capabilities. His name derives from Sanada Masayuki, the historical Japanese daimyō renowned for military strategy during the Sengoku period.