How could advanced civilizations not know about God and be actively working against you?

It is really no different than your own civilization and the current state of affairs with respect to level of belief. While the majority of people will identify themselves as religious, relatively few are applying themselves diligently to regular interaction with the divine realm in a meaningful way. And this is because of the corruption of religion to disempower people, and while holding up the image of the divine realm, keep the people somewhat disconnected, and so the yearnings are there but not the encouragement to embrace the divine realm in the highest and best way. You can see that given more time, humanity will likely move in the direction of increasing disbelief and secularization and the eventual abandonment of formal religion altogether, and moving towards a further embracing of technology as the answer to human betterment. This is the precise sequence that befell the extraterrestrial civilizations now preying upon humanity. They were corrupted by fallen angelics who then began to cause a rejection of the very idea of God, and over a great span of time, this became quite well entrenched to the point where any idea of a divine agent or source is unthinkable.