Sometime after his fall into darkness, Ultraman Tregear created Reugosite by corrupting Space White Blood Cell's genetic code, repurposing it into sentient doomsday weapon to kill all life and importantly, as part of the war against Ultras. The monster soon confronted by Ultramen Rosso, Blu and Grigio, who attempted to use their Gyros to convert it into a solid form so they could destroy it. Only managed to convert its form to an intermediate state, the Ultramen brought their fight into a wormhole which transported them to Earth. Attempting to devour the nearby planet, it was driven away by the siblings at the cost of Rosso and Blu's lives.
After AizenTech detected that Reugosite would return to Earth soon, Saki Mitsurugi began plotting to destroy it by turning the Earth into a giant bomb.
Though Reugosite was imprisoned in an R/B Crystal by Mio Minato, who attempted to get rid of it by throwing it into the dimension she was previously trapped in, Saki stole the crystal from her, believing her way was the only solution to destroy Reugosite. However, after Saki defeated Ultraman Ruebe as Grigio Regina the R/B Crystal activated itself and freed Reugosite.
Reugosite then went on a rampage destroying everything in its path. Saki attempted to hold it off as Grigio Regina while AizenTech also tried to restrain the monster. Reugosite managed to overpower Grigio Regina but before he could finish Saki off with his Genesis Requiem his attacked was blocked by Ultraman Rosso and Blu. Reugosite then fired another beam at the brothers but the attack was blocked by Grigio, who sacrificed herself to save them.
Rosso and Blu then transformed into Ruebe to fight Reugosite but were still overpowered by the beast. Before they could be finished off by it however Mio forced them out of their transformations. Rosso and Blu later went to fight the monster again and became Ruebe, though even with their best efforts they were initially not able to beat back the monster. However, after Asahi transformed into the Makoto Crystal, the brothers finally destroyed Reugosite with the Shin Vortex Buster, unknowingly halting Tregear's destructive plan.