Keep in mind, these 'gatekeepers' are usually morally strong. They kill those who need to go, whether to end suffering or in justice of a major wrong doing. They walk among the streets as humans, making sure these deaths look natural, or like an earthly accident. Now what would make them want to wipe out all of human kind?
closed as off-topic by Separatrix, sphennings, Frostfyre, Mołot, Azuaron Jul 13 '17 at 13:26
This question appears to be off-topic. The users who voted to close gave this specific reason:
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The humans may have advanced to a point where the gatekeepers can no longer remain hidden and manage "the herd" from the shadows. Maybe normal humans are increasing in their mastery of the magic of clairvoyance or prophecy, making secrets a thing of the past.
If the gatekeepers know that we are not yet morally evolved to manage ourselves and yet they also know that they can no longer manage us, they may choose to end us rather than loose our evil upon the world.
As you state, they are morally strong.
They see humanity is more and more corrupted as the time passes by and fewer and fewer righteous men are seen over time. One day they see something which drives them nuts (i.e. a child killing another one for having refused giving a candy) and they decide mankind cannot be saved anymore. The only solution is to whipe them out and start over again.
So it begins...
A society forms in which civilization is dependent on its leaders; without the threat of the law, most people will cheat and steal, making it pointless for anyone to grow food (since it will be stolen anyway). The population has grown to the point where hunting and gathering is no longer sustainable; so if the farms disappear society will dissolve into chaos.
But the position of leadership - which is necessary for survival of the society - tends to attract the corrupt, and corrupt those who take it. If the current leader is killed, an even more ruthless one will climb to the top. Now the Gatekeepers have to choose to either let the corrupt leadership live, or kill every leader, one after another, and watch the civilization fall apart...
Mass Extinction of Other Species
Especially where those species approach something resembling consciousness.
You could use the current, ongoing, Holocene Extinction as a blueprint.
Every morality has it's precepts, if the guardian species have a precept that dictates that all life is valuable, they may have a threshold where it becomes necessary to eradicate one species, to save many others.
Morally, humans have a culpability that comes in when it becomes explicitly clear to humans that avoidable extinction is happening, yet the course is not altered.
A variable parameter in this would be to what extent the guardians have an anthropocentric/sapience-oriented hierarchy of the value of life on earth, as most humans do. Our value places us at the top, which is zoologically typical as far as I know. However, there's no rule saying that your guardian species would do likewise.
Maybe they're guarding us now, and the vaquita is their favourite animal?
ps: your question put me in mind of Doomlord - a kids comic that did something similar, which I remember fondly.
If you don't mind if the background of the gatekeepers gets twisted, then another premise you could consider is that the gatekeepers use humans as an (unwitting) tool to build all kind of structures and invent new technology.
Humans that act destructively should then be removed (by means of assassination) from the environment, simply because they potentially slow down progress.
Mass murder occurs when the gatekeepers decide that want to claim the resources that humanity has made 'for the gatekeepers'. They could clear an entire continent to use for a purpose of their own (a pet project?). If the remainder of humanity becomes a problem that is no longer worth the effort, they might even want to resort to genocide.
Humanity has discovered the cure.
The cure to what, you say? Why, the cure to everything known of course. Death is no longer part of a human life and there is no "life cycle" anymore. The keepers see that humans have advance far too much and they know that they will be an uncontrollable pest upon the universe or worse, wipe themselves and all life on Earth.
So they decide to take action. They make a genetically engineered virus (if they can) or do it in a fantastical / magical way and release it into the air. All of humanity becomes sick in a matter of days and they die off. This way, you can also keep people alive that matter to the story by giving them immunity to the virus.
You could also say that, since humans are no longer dying, the gatekeepers went mad with nothing to be done around them. Maybe the gatekeepers were dependent on "the last breath of a human" to keep living, so they had to do something to restart humanity but not necessarily wipe them off.
Alternatively, any modification you make on these reasons or methods, or a combination of them, is also applicable.
The Keepers had MISSED something that had already become too ingrained to control with surgical removals.
Their understanding of our nature no better than ours, they have only recently identified it as a phenomenon to keep an eye out for, and only now come to realize it is too late to control it. Like a symptomless disease that presents a danger they cannot allow. Or a psychological quality.
Their "pruning" activities are of course limited: life is valuable, mass "accidents" are implausible, and the Keepers often give the benefit of doubt - humans are, after all, weak, easily manipulated, and all too rarely does their environment leave the opportunity to have have strong, properly developed moral beliefs.
When such beliefs DO exist, though, it is an abomination in the Keepers' eyes for a subject to shove them aside for no apparent reason.
And then along comes Stanley Milgram and shows 65% of people will torture a man to death just because they're repeatedly asked to in a calm voice.
No, this cannot be.
How can they! How could WE have missed it!?
We can salvage this. We'll work harder, and overcome the...
...the INSURMOUNTABLE difficulty of developing and spreading an evolutionary DISADVANTAGE, with what? A Death Note?
Bring out the backups.