“I know what it's like to lose. Feeling so desperately that you're right, but fail all the same. You can dread it. You can try and hide from it. But destiny still arrives. You see, fun isn't something one considers when balancing the universe. But this does put a smile on my face.”
The Other tells Thanos that the Tesseract is on a small world, a human world. It also informs him that Loki is ready to lead the Chitauri.
In a post-credits scene, Thanos is revealed to have been Loki's benefactor, having provided the Chitauri army used by Loki in his attempted invasion of Earth. When advised by his intermediary (known simply as the "Other" ) that opposing the Avengers would be "to court death", Thanos glances at the camera and flashes an evil grin.
Thanos plays a more active role in the film, where he has enlisted the help of Ronan, Korath, and his daughters, Gamora and Nebula, to retrieve the Orb for him. As it turns out, Gamora is not actually Thanos' daughter, since Thanos killed Gamora's family and snatched her as an infant to train her into the perfect assassin, having abused and tormented her in the process of doing so. This causes Gamora to betray Thanos, which leads to a chain of events that leads to Gamora finding her true calling as a protector of the universe and a member of the Guardians of the Galaxy.
When Ronan and Nebula are called to discuss Gamora's betrayal, Ronan kills The Other, who was speaking for Thanos. Thanos does not react to this but is angry at Ronan for not obtaining the Orb (and for apparently alienating Gamora). He says he will destroy Xandar for Ronan if he brings him the Orb, and will kill him if he does not.
Thanos promised Ronan that he will help Ronan destroy Xandar in exchange for Ronan's services. However, once Ronan gets ahold of the Orb, he feels he no longer needs Thanos help and also decides to betray him. Nebula also decides to betray Thanos out of jealousy over Thanos showing preference for Gamora over her. Ronan and Nebula take Korath with them. In the end, Ronan and Korath are killed by the Guardians of the Galaxy (including Gamora), Nebula escapes and becomes a renegade villain independent of Thanos, and the Guardians give the Orb to the Nova Corps for safekeeping.
Thanos, however, is still determined to find the six Infinity Stones and the Infinity Gauntlet so he can use them to conquer the universe.
Thanos will directly serve as the primary antagonist of this film, having finally collected all Infinity Stones, and combating against the reformed and expanded Avengers, allied with the Guardians of the Galaxy.
At the end of Season 1 finale The Final Showdown, Thanos is revealed to be Red Skull's master as Red Skull gives him the Tesseract. In the final moments of the episode The Arsenal, Thanos comes to Earth in search of the Power Stone.
In Season 2, Thanos is the overarching primary antagonist, sharing the role with Ultron and the Squadron Supreme.
In Thanos Rising, after attacking the headquarters of Uatu, Thanos shoots down an Avengers Quinjet. After falling into a trap of the Avengers, Thanos confronts the Avengers, Thanos wins easily but Arsenal hits him with the power of the Power Stone. However, Thanos reveals that is in possession of the Infinity Gauntlet and takes the stone from Arsenal.
The Avengers manage to belay Thanos, who is defeated when Arsenal unleashes the power absorbed by the stone, blasting Thanos halfway across the galaxy.
At the end of Widow's Run, after a debacle with Dormmamu and Black Widow with the Infinity Stones, Thanos finally returns to Earth at the last minute, and claims the Stones, assembling them into the Infinity Gauntlet. Retreating into space, the Avengers pursue him. In Thanos Triumphant, Thanos begins to use the Stones to construct a shrine for himself above the Earth, and with a wave of his hand, wipes out dozens of stars. However, the Avengers, using Titan technology, charge towards him. While using Titan battle suits, the Avengers are no match for the Infinity Gauntet's power. Thanos effortlessly trashes the mechs, and the Avengers take him head on.
Although the main antagonist of Avengers: Infinity War, Kevin Feige as described him as essentially being the main character as he will have a major role and it will explain his motivations for his actions.