R3-S6 was a masculine programmed R3-series astromech droid manufactured by Industrial Automaton on the planet Nubia around the time of the Clone Wars. On his homeworld, R3-S6 was stolen by a group of agents hired by CIS General Grievous. They took R3-S6 to the planet Milagro where the astromech droid underwent reprogramming to become a spy for Grievous. The reprogrammed R3-S6 was sold to the Galactic Republic to become Jedi General Skywalker's replacement astromech droid. R3-S6 accompanied Skywalker and Commander Tano, as the two Jedi searched for Skywalker's previous astromech droid in the remnants of the Battle of Bothawui in Bothawui space. When the group came across a Trandoshan scavenging freighter in the battle aftermath's debris field, R3-S6, Skywalker, and Tano boarded the vessel to find R2-D2.
After the unsuccessful search aboard the freighter, R3-S6 and Skywalker embarked on a new mission to sweep through suspected CIS space. The operation was thwarted by Grievous, who tracked Skywalker via the Jedi General's starfighter homing beacon, though R3-S6 and Skywalker were rescued by the timely arrival of Tano aboard Skywalker's freighter. Inside the ship, R3-S6 and Tano received a transmission from R2-D2, and Skywalker ordered them to track the signal which led the group to Skytop Station, a CIS listening post. In the station, Skywalker went to find R2-D2, while R3-S6, Tano, and a group of clone troopers left to destroy the station's reactor core. R3-S6 watched as Grievous confronted Tano's group and attacked Tano, though the Commander retreated with R3-S6 to a storage room. As the Commander hid from Grievous in the room for some time, Tano spotted R3-S6 conferring with Grievous and found out the droid's true allegiance. The droid soon left Tano, and found Skywalker in the base's hangar, who also found out that R3-S6 was a spy droid. R3-S6 was destroyed when he was hit by flying debris after a brawl with R2-D2 on a catwalk outside the listening post.