Doctor Strange in the Multiverse of Madness pits two powerful Avengers against each other and sees the Scarlet Witch deliver a devastating defeat to the Illuminati. The Scarlet Witch also handed the Avengers terrible losses in Marvel Comics, including tragic events like House of M and Avengers: Disassembled. The team often works as their own worst enemy, as seen in the Civil War comic book storyline.
The Avengers lose many times in Marvel Comics, often paying a steep price for saving the day. Their biggest losses usually come at the hands of all-powerful villains that prove too much for any foe, like Magneto or his psionic doppelganger Onslaught. Much as they did in the MCU, the Avengers also proved no match for Thanos and the Infinity Gauntlet, though they never give up despite the overwhelming odds.
The Avengers successfully fend off a global attack by the Skrulls in Secret Invasion, but in many ways, they lose. The fallout from the invasion includes a complete public collapse in confidence in the team, allowing Norman Osborn to swoop in and replace them with the Dark Avengers in Dark Reign.
Osborn inserts supervillains in place of former Avengers, with Bullseye replacing Hawkeye, Moonstone replacing Ms. Marvel, and his taking Iron Man's place as Iron Patriot. The Avengers' corruption at the hands of a powerful villain serves as a terrible defeat and one that may be occurring in the MCU with The Contessa slowly acquiring an alternate Avengers slate in U.S. Agent and Yelena Belova.
Onslaught
Onslaught ranks among the most powerful supervillains ever, with the combined power of Professor X and Magneto. He used that power to crush the Avengers in the 1990s, devastating them so completely that Franklin Richards shuttled them to a pocket universe to save their lives.
The Avengers and Fantastic Four both fell to Onslaught after coming to the X-Men's aid. They remained in the pocket dimension for a year, with everyone in Earth-616 believing they had died in battle against the all-powerful villain.
Ultimatum
Ultimatum features the most shocking deaths in Marvel Comics, with grizzly ends for a number of Avengers including The Wasp and Doctor Strange. Magneto delivers a crushing blow to the team in Ultimatum, a dark crossover in Ultimate Comics.
The story begins with Magneto unleashing a tidal wave against New York City, destroying it, and killing many superheroes including Daredevil. He goes on to wage an all-out war against the Avengers and X-Men, decimating both teams.
Old Man Hawkeye
Old Man Hawkeye #7 reveals the Avengers' brutal fate in the nightmarish alternate reality of Old Man Logan. The team goes down one by one as Clint Barton watches, losing their lives to allied supervillains like the Red Skull and Magneto.
Hawkeye's Thunderbolts team turns on him, reverting back to their villainous ways as the Masters of Evil, and things only get worse. Hawkeye survives the devastation, but he carries great guilt and sadness with him into the dystopian future that follows.
Age Of Ultron
The Avengers rarely fare well in alternate timelines. The Age of Ultron comic book storyline presents one of the darkest Marvel Comics timelines, in which the evil android takes out the team and takes over the world with his drone army.
Ultron killed many Avengers in the process, including Janet Van Dyne who served as Captain Marvel in this reality. She and Captain Britan died defending London, and other members including She-Hulk and Black Panther also fall before Ultron is defeated.
Under Siege
Comic book fans know Baron Zemo counts among the most powerful Avengers villains and Under Siege is perhaps his crowning achievement. Zemo leads the Masters of Evil in an all-out assault on Avengers Mansion, destroying it in the process.
The Masters of Evil also brutally attacked Jarvis, the team's butler, leaving him with life-threatening injuries. This 1980s storyline represents a colossal defeat for the Avengers considering the firepower on the team, including Thor and Monica Rambeau as Captain Marvel.
Avengers: Disassembled
Avengers: Disassembled sees the Avengers losing to one of their own. The Scarlet Witch discovers Agatha Harkness placed a spell on her to make her forget her children ever existed, leading to Wanda's near-total destruction of the team.
The Scarlet Witch kills Agatha in a fit of rage, and then rampages through the Avengers, leading to Hawkeye's heroic sacrifice. The 2004 storyline counts as one of the Avengers' worst losses and inspired in part Wanda's dark turn in Doctor Strange in the Multiverse of Madness.
House Of M
The Scarlet Witch delivers the Avengers another staggering loss in House of M, a consequential storyline for the team and the X-Men. The Avengers fail to stop Wanda from altering reality to bring her children back, and that's just the start.
A new Avengers team led by Luke Cage forms in Wanda's altered reality, but they prove as powerless as anyone else against the Scarlet Witch. She lashes out, erasing all but a handful of mutants from existence and driving a wedge between the Avengers and X-Men.
The Infinity Gauntlet
The Infinity Gauntlet begins with Thanos snapping his fingers and erasing half of all life in the universe. This cuts the Avengers down to their bones and their initial response to him leads to even more loss when he destroys Captain America, Thor, and the Scarlet Witch.
Unlike the MCU, the comic book storyline discards the Avengers largely from the opening pages, leading other characters including the Silver Surfer and Adam Warlock to attempt to stop the Mad Titan from continuing his cosmic rampage.
Civil War
Civil War in many respects represents the worst Avengers loss in Marvel Comics, as the team defeats itself. The Superhero Registration Act divides the team into two warring factions headed by Iron Man and Captain America, leading to disaster.
The conflict pits friends against friends and heroes against heroes, with the ultimate battle an all-out brawl in New York City. Captain America stands down, wanting to avoid any further destruction, and ultimately loses his life to an assassin in the story's coda.