ABC's Agents of S.H.I.E.L.D. is inching closer to being recognized as the official Marvel Cinematic Universe canon. The recent Phase 5 Disney+ series Echo confirmed that each of Marvel's Netflix series is canon, leaving only the franchise's network shows to be officially recognized in the same manner.

Agents of S.H.I.E.L.D. ran for seven seasons from 2013 to 2020, occasionally tying into various MCU movies. Just under the radar of the larger MCU, the show's characters faced plenty of major threats over the years. In its celebrated run, the series introduced several villains whose terrible evil measures up to even the powerful villains of the larger MCU movies.

Updated by Jordan Iacobucci on May 3, 2024: The Marvel Cinematic Universe is bringing back old series like Daredevil, causing many fans to year for an Agents of S.H.I.E.L.D. revival. With increased attention paid to the show in recent months, fans are reliving what made it such a special series, including its epic and dangerous villains.

15 Agent 33 Just Wanted Closure

Agent 33 was an agent of S.H.I.E.L.D. who was captured and brainwashed by Daniel Whitehall in Season 2. After her brainwashing, Agent 33's face was fused to a digital mask capable of replicating any face, making her a serious threat to S.H.I.E.L.D. She eventually teams up with the traitorous agent Grant Ward, who tries to help her reclaim her old identity.

Agent 33, whose real name is revealed to be Kara Palamas, is a truly tragic figure. Once a loyal agent of S.H.I.E.L.D., she was turned into a villain against her will. Even worse, she allowed herself to be manipulated by Grant Ward into thinking that she needed closure by killing the agents who never came to save her. In the end, Kara suffers a tragic death that underscores how far she has fallen since her noble stand against Daniel Whitehall. She may not be the show's most fearsome villain, but Agent 33 is certainly one of the most tragic.

14 Jasper Sitwell Was A Great MCU Tie-In

Jasper Sitwell was an agent of S.H.I.E.L.D. revealed, along with many of the organization's other operatives, to have been working for Hydra all along. His character only makes a few brief appearances in the first season of Agents of S.H.I.E.L.D. before his death during the events of Captain America: The Winter Soldier.

Despite technically taking place in the franchise's timeline, Agents of S.H.I.E.L.D. is rarely substantively connected to the Marvel Cinematic Universe. Jasper Sitwell's involvement, however, helped connect the series to the larger MCU while also setting up his villainous reveal in later projects. While his impact to the story may have been minor, Sitwell is a nice connector between Agents of S.H.I.E.L.D. and The Winter Soldier.

13 Daniel Whitehall Was A Callous And Cruel Scientist

Daniel Whitehall is a villainous Hydra scientist with a particular fascination for the long-fabled Inhumans. Through callous human experiments, Whitehall studied the Inhumans over a period of decades until his eventual death at the hands of Agent Phil Coulson in Season 2 of Agents of S.H.I.E.L.D.

Whitehall's calm and callous demeanor while committing unspeakable atrocities against mankind makes him one of the show's most terrifying early villains. While Whitehall himself is not the main villain of Season 2, his awful experiments corrupted Jiaying, turning her into the villain that nearly destroyed S.H.I.E.L.D.

12 Raina Had A Terrific Redemption Arc

Raina is one of Agents of S.H.I.E.L.D.'s most enduring villains. First introduced early in the first season, Raina worked with both the Centipede Project and Hydra, particularly looking for artificial superpowers. After pursuing the Inhumans for a long while, Raina herself is transformed into a spiked Inhuman and taken to the safe haven known as Afterlife.

Originally one of the biggest thorns in the sides of Agents of S.H.I.E.L.D.'s main heroes, Raina had a surprising redemption arc after being turned into an Inhuman. The character slowly began to see the error of her ways and even goes on to heroically sacrifice herself near the end of the season.

11 Ruby Hale Was A Tragic But Terrifying Figure

Dove Cameron has a guest arc in Season 5 of Agents of S.H.I.E.L.D. as Ruby Hale, the daughter of the villainous General Hale. Trained as a human weapon since childhood, Ruby is callous and uncaring when it comes to attacking other human beings, leaving a permanent mark on the Agents of S.H.I.E.L.D.

Ruby is perhaps best known for her fight with Elena "Yo-Yo" Rodriguez, in which she left the Inhuman without arms, altering her life forever. This prompted much of Yo-Yo's arc in Season 5, culminating in her callously killing her young enemy, shocking the other members of Coulson's team and taking Yo-Yo to a dark place in future episodes.

10 John Garrett Was Twisted And Treacherous