Doctor Strange in the Multiverse of Madness shows the Sorcerer Supreme at his most powerful but also hands him a major defeat. He fails to stop the Scarlet Witch from destroying Kamar-Taj or killing the Illuminati, and he ultimately isn't the one who brings an end to her rampage. Doctor Strange suffers even greater losses in Marvel Comics.
Though Doctor Strange possesses unmatched power and knowledge in the mystic arts, he doesn't always save the day. Strange loses many times in the comics and he often plays a hand in his own defeat. Sometimes his arrogance blinds him, as it does with the Illuminati, and sometimes, he gives in to his worst instincts and the allure of greater power. He also loses to far more powerful foes, including the Scarlet Witch in the House of M epic storyline.
Sise-Neg
Marvel Premiere #14 represents the culmination of a standout storyline from writer Steve Englehart, who pits Doctor Strange against Sise-Neg. This malevolent entity goes backward in time, absorbing all mystical energy as he goes, and Strange fails to prevent him from destroying the universe and then recreating it.
The story ends with an intriguing question though, as Strange and the present day persist. Did Sise-Neg create the Big Bang when he went back in time? Was Strange's loss reality's gain?
Losing His Eye
Doctor Strange possesses unimaginable skill and power in the mystical arts, but he doesn't always escape clean. In Strange Tales #10, Doctor Strange loses his eye to the demonic entity known as Ghaszaszh Nyirh. Strange wears an eye patch after failing to mend his injury with magic.
Ghaszaszh Nyirh appears in the guise of Clea in this storyline. Comic book fans know Clea studies under Strange and ultimately becomes his wife in the comics, as she may in the MCU.
No Longer The Sorcerer Supreme
Doctor Strange loses the title of Sorcerer Supreme in Doctor Strange: Sorcerer Supreme #48, among the best 1990s Doctor Strange comics, when he refuses to fight a war for the Vishanti, the powerful mystical beings whose power informs much of his. The Vishanti strip him of the title but he continues to practice magic and defend the world from threats.
He joins the Midnight Sons during this period, as he may do in the MCU. Strange no longer holds the title in live-action as well, though due to vastly different circumstances.
Marvel Zombies
Doctor Strange loses his life in the Marvel Zombies comic books, though his misery doesn't end there. Strange uses his powers to fight off the zombie hordes in this alternate reality, but he eventually succumbs. A zombie bites him and he becomes a zombie himself, with complete agency and use of his magical talents.
Zombie Strange later joins forces with other undead heroes and villains to hunt down the last remaining uninfected. He also helps the Zombie Kingpin find other universes to continue their hunt in.
Erasing Captain America's Memories
Doctor Strange succeeded in wiping out Captain America's mind, but he lost much of his integrity in the process. Strange prevented the Avenger from stopping the Illuminati's efforts to prevent incursions from destroying the Marvel Universe after Captain America objected to their use of a superweapon to do so.
Comic book fans know the Illuminati make hard choices often with little regard for who they affect. Strange participated in several such situations, including exiling Hulk to Sakaar.
Disciple Of Dormammu
Doctor Strange defeated Dormammu in the MCU, but in What If? #18 from 1979, he becomes the malevolent entity's disciple. Strange abandons his oaths and his principles, losing his soul in the process. He studies under Dormammu, ruler of the Dark Dimension and among Doctor Strange's most powerful villains.
Strange later turns on his master, choosing to fight alongside the Ancient One instead, but the damage is done to his character and integrity. Strange murders Mordo to take his place at Dormammu's side.
House Of M
Doctor Strange numbers among the heroes trying to help Wanda in House of M, though his lack of bedside manner likely contributes to her agitation. Despite his power and attempts at intervention, Wanda alters reality to bring her children back to life and mitigate any further threats to them or her peace.
Doctor Strange changes with everyone else in her new altered reality and though he regains his memory of the real world, he ultimately loses in his bid to stop her from lashing out. She erases most mutants from existence in retaliation for the X-Men and Avengers shattering her reality.
Secret Wars
Doctor Strange loses his reality and agency once again in the 2015 Secret Wars crossover event. Doctor Doom steals the power of the Beyonders and collapses the multiverse down to one reality, Battleworld. In this new reality, Doom makes Strange his personal assistant, a humiliating defeat for the Sorcerer Supreme.
Strange eventually regains his agency and helps the resistance fight back against Doom, but he loses his life in the process. He returns to life when the multiverse is restored at the story's end.
Ultimatum
Strange suffers perhaps his most gruesome loss in Ultimatum, an apocalyptic crossover event that upended the Ultimate Comics universe, Earth-1610. During the event, several supervillains exploit Magneto's destruction of New York City via a tidal wave. In the story, Dormammu horrifically kills Strange in the Sanctum Santorum.
This Doctor Strange variant followed a different path to the mystic arts. His father married Clea but then vanished before he was born, leaving Wong to train Stephen Strange Jr. in magic.
The Death Of Doctor Strange
Recent comics dealt Doctor Strange a serious loss in Earth-616. The main Marvel Universe Strange died, with his murder a confounding mystery. Clea takes his place as the new Sorcerer Supreme, realizing her tremendous knowledge, experience, and power as his former student and the niece of Dormammu.
Doctor Strange remains dead for the moment in the comics, though he's certain to return at some point. In the meantime, Clea makes efforts to resurrect him, though it proves difficult even with her skill.