- Plague Knight - Leader of the group, head alchemist and mole inside the Order of No Quarter
- Mona - Second in command, head researcher and mole inside the Village
- Percy - Mechanic, researcher, and philosopher
- Magicist - Supporter and mole inside the Village
- Oolong - Mascot of the group and provider of musical entertainment
- Mail Minion - High ranking minion and postman
- Hedge Pupil - Disciple and mole inside the Village
- Plague Minions - Indistinguishable grunts, all-around factotums and occasional test subjects
In addition Baz later was recruited as a Plague Minion of questionable usefulness, after Plague Knight defeated and took pity on him. Furthermore the Explodatorium staff (such as the Alchemeister), being directly under the employment of Plague Knight, can trace back their origins in this group.
Due to the study of alchemy being seen with suspicion by the general populace, Team Plague had a poor reputation in the Valley, with rocks regularly thrown at them. As such many of its members preferred to hide their affiliation with the group, like Mona and the Magicist. Due to her high status within the Village, the Magicist in particular is noted by some Plague Minions of taking a big risk helping them. After Plague Knight forceful admission into the Order of No Quarter, his reputation further sank, being banned altogether from the Village and pursued by the Knights of the land. However Plague Knight took this as an opportunity and, together with Mona, began planning to harvest the Essences of his fellow Order members and its leader to create the Ultimate Potion, a legendary concoction said to grant any wish its drinker desire and regarded as the ultimate achievement for any alchemist. Unbeknownst to anyone except Plague Knight himself however, the alchemist began desiring the potion in hopes that it could improve him just enough to be worthy of Mona's affection. To this end, Plague Knight and Mona constructed a complex secret base underneath the Village, the Potionarium, accessed from the backroom of the Juice Bar via Torque Lifts.
After the swift conquest of the Valley by the Order, Plague Knight set in motion his plan, unknowingly aiding Shovel Knight in his personal quest, and even single-handedly claiming the Armor Outpost for himself.
Plague Knight had also to briefly visit the Explodatorium which, due to his absence, was plunged into chaos, with experiments running amok and the majority of its staff revolting. After putting his disloyal minions back into place, Plague Knight confronted the intruder who sneaked into his facility, Shovel Knight and decided to collect his Essence.
However, due to the interference of Black Knight, who guessed Plague Knight's plan but misunderstood its final purpose, Mona felt betrayed and left the group, leaving her duties to Percy and breaking Plague Knight's heart.
Eventually, Plague Knight efforts, united with Shovel Knight actions, resulted in the defeat of the Enchantress. Thanks to Black Knight's unexpected aid, Plague Knight and Mona made amends with each other and confessed their mutual feelings. Together they decided to detonate the now concocted Ultimate Potion, causing a massive explosion that collapsed the Tower of Fate.
This action earned Team Plague the gratitude of the people, ailing them as heroes, and letting them practice their studies without fear of persecution. Plague Knight also decided to leave the Explodatorium under the management of the Hedge Pupil, Percy and the Magicist.
- One of the major reasons as to why the Alchemists are seen with suspicion and disdain from the majority of the Valley population is implied to be because they produce fool's gold from sawdust and mouse skulls and sometime use it in place to genuine gold as they don't see any differences between the two, leading the common folk to see them as cheating thieves.