The Guardians Of The Galaxy have saved the Marvel Universe more times than anyone can count. They've gone out and faced the worst of the worst, from Thanos, Ultron, and Nebula to the Cancerverse, Mr. Knife, and the Shi'Ar Empire. Despite that frightening rogues' gallery, they've come out on top...most of the time.
Even the Guardians have their bad days, and they've lost many battles as well. They take on threats to the entire galaxy and, sometimes, the universe. Their foes rank among the most powerful in the Marvel Universe, and some are practically gods. Every once in a while, those enemies bring the Guardians of the Galaxy to their knees.
10 Yotat
The first entry into this list comes from Secret Wars (2015) where the Guardians charged themselves with defending Knowhere, which then orbited Battleworld. Yotat was an intergalactic hitman with a grudge against the Guardians that survived the universal collapse that came with Time Runs Out.
He wanted vengeance on the Guardians of Knowhere for a defeat he received at the hands of Rocket Raccoon and Drax the Destroyer. Yotat, who had been transformed by a chemical explosion, came back as a massive muscle-bound bruiser, and he ambushed the Guardians of Knowhere and defeated them single-handedly.
9 J'Son
J'Son is the father of Peter Quill and Emperor of the Spartax, and he has held a grudge against the Guardians of the Galaxy since his son refused to accept his position as the heir to the Spartax throne. With but a word, he was able to order the Guardians arrested by an intergalactic police force, but the Guardians escaped.
However, J'Son had them captured separately and brought to Spartax. This would have been the end for the Guardians if Captain Marvel hadn't later arrived to rescue the team.
8 Thane
After being deposed by his own son, J'son took up the name Mister Knife, formed a crew, and began searching for an artifact called the Black Vortex. This mirror-like device shows a person their full potential and then turns the subject into that version of themselves.
J'Son showed the Black Vortex to Thane, and it vastly increased his power, particularly his ability to encase a victim in "living death." He took on the Guardians on Spartax, and they were unable to stop him from using his living death ability to encase the entire planet.
7 The Vision
"Defeat" can mean many different things, and, in this case, it means humiliation. The Guardians of the Galaxy helped their teammate, Captain Marvel, during the Civil War II battle at the S.H.I.E.L.D. Triskellion headquarters.
During this battle, the Guardians used their ship to aid their side, and the Vision destroyed it with a stray energy blast. Unable to access another way off the planet, the Guardians were left grounded and split apart for a while due to some unresolved issues.
6 Thanos
Unsurprisingly, the Guardians of the Galaxy haven't won all their conflicts against the Mad Titan. Two instances come to mind as far as Thanos single-handedly defeating the team. The first came when the Guardians teamed up with the Avengers to stop him from using the powers of a Cosmic Cube.
During the fight, Thanos expelled both the Guardians and the Avengers to what turned out to be the Cancerverse with but a thought. The latter instance also took place in the Cancerverse when Star-Lord and Nova had to stay behind in the collapsing universe to keep Thanos from escaping and terrorizing the Marvel Universe once more, effectively ending the Guardians of the Galaxy until Quill's return.
5 Zeus
More recently, Star-Lord united a Guardians of the Galaxy team with Rocket, Nova, Phyla-Vell, Moondragon, and Noh-Varr to stop a resurrected Greek Pantheon's brutal path of destruction.
However, the team was unable to put a halt to Zeus and the Pantheon and were forced to retreat while their world ship's teleportation device subsumed the Pantheon and Star-Lord.
4 Mar-Vell
Like the prior entry, the phrase "all by themselves" is being stretched a bit here, but the Mar-Vell of the Cancerverse helped end the Guardians of the Galaxy. His invasion into our universe left the Guardians so desperate that they had to work with Thanos to slay the Cancerverse Mar-Vell in his own realm.
This led to Peter Quill and Richard Rider staying behind to stop Thanos from escaping and leaving the Guardians of the Galaxy without their leading figures. The team ended for a time after this.
3 Gamora
Gamora turned on her Guardian allies and became Requiem when she discovered that a part of her soul was trapped inside the world of the Soulstone.
During their confrontation, she used the Infinity Stones to slay the Guardians and a portion of the Avengers in Central Park--going so far as to impale Star-Lord--which was only being undone through the timely use of the Time Stone. However, this still left a longlasting scar that would end to a disbanding of the Guardians of the Galaxy.
2 Michael Korvac
This defeat was bestowed upon the other Guardians of the Galaxy--the ones from the 31st Century. Once again, the Guardians teamed up with the Avengers to stop the universal threat that was Michael Korvac, a being from the 31st Century with godlike power.
He was able to slay every member of the Guardians of the Galaxy and the Avengers with his powers. This was only undone by Korvac after he was betrayed by a lover, and Korvac proceeded to wipe himself from existence.
1 Star-Lord
Peter Quill has proven himself a worthy and dedicated leader of the Guardians of the Galaxy, but his recklessness has led to the downfall of the Guardians in the past. He's even let his ego and grudges bring the team to the brink on several occasions. And, he also ended the team once.
After the betrayal at the hands of Gamora and Drax departing to help Adam Warlock and Kang the Conqueror to handle a new Infinity Stone crisis on the horizon, Star-Lord proclaimed that the Guardians of the Galaxy were over before binge-drinking himself into a depressed stupor.