The guardians are old flood defense mechanisms. Chief is activating them so that Cortana in the domain can use them, cuz it turns out a fully corrupted Didact is leading the flood against the galaxy. ONI wants to use them to wipe out the rest of the elites while they're at their weakest, but Osman gets kilt by Chief and Halsey. Locke takes over ONI.
The main story revolves around Chief trying to figure out why Cortana(!!) is drawing all these Guardians to her - which is destroying colonies as they leave. Locke is sent after Chief to bring him in not just because he left despite orders, but because Halsey thinks Chief wont' stop Cortana. Cortana ends up cured of Rampancy because she gained access to a Forerunner thing called the "domain" and asks any AI to join her cause. Tons do and they get cured of rampancy as well. So her master plan is to use Guardians as they were intended - giant planet police bots. Obey her laws, obey the peace, or else these massive things will murder. Chief tries to talk her down, but she doesn't listen and imprisons him in the same kind of thing the Didact was inside in Halo 4. She says she'll wake him up in 10,000 years. Locke tries freeing him, but the AIs join Cortana, she sends out all of her Guardians to planets, she's leaving on the like biggest Guardian and Locke frees Chief just as she's leaving. The AIs wipe out the electronics in all the stations and colonies they oversee. Roland (Infinity's AI) does not join Cortana. She finds Infinity, and they have to flee into slipspace repeatedly. Game ends as they are fleeing until they can think of a plan. Next cutscene is reunion between Halsey, Arbiter, and Chief. Short one, and that was about all there was to it. Final cutscene after credits is Cortana humming a tune, and a Halo ring in the distance. As she finishes humming, the lights on the Halo light up as if she's getting it all powered up again. So yeah, basically ends there almost on a cliffhanger - Cortana is a bad guy, planets everywhere are under siege by an impossible force to counter, and Cortana owns a Halo ring.
She doesn't hate Chief. She thinks he'll come around to it. She thinks that perfect peace is worth it, but she's ignoring the casualties of her actions. Blue team brings this up with Chief. Chief tells her that she's trying to improve people without giving them a choice - like what Halsey did to him. Cortana doesn't listen, basically. The main "bosses" you fight, are the same dude with tons of bodies. He guards the Guardians/Cortana. He wants to prevent Chief from getting to Cortana, and Cortana does not want him to kill Chief. So they argue. But yeah this Warden Eternal has a bunch of bodies. You fight one at once, then later two at once, then in the hardest fukking fight ever 3 at once without much cover at all. Absolutely brutal fight. Cortana also sounds different a bit. More robotic than she used to. However, she might also be in physical form now. Early in the game it's referenced she will be able to eventually, and near the end she seems to be glowing, but then the glowing parts fade - almost like they were a shield rather than her normal body details. Apparently, Locke was an assassin who once came up with a plan to kill Arbiter until "things changed". So I wonder if in Halo 6 Locke is sent to kill Cortana, and Chief wants to not only prevent that, but stop her actions too. Definitely reminds me of Halo 2's cliffhanger ending, not so much as it interrupts the story midway ,but really not much was resolved haha, and it feels like it was all a leadup to next game.