Is Agriculture. Or rather choosing to increase food production over limiting growth.
According to Jared Diamond, when our hunter gatherer society start to grow in population at the end of the ice ages, we chose agriculture to feed increasing number of people rather than limiting our population growth. This move has created problems that we still haven't learnt to solve, while the continued presence of hunter gatherer societies after tens of thousands of years proves the viability of the model.
So what are the problems that agriculture has caused for us for it to be the biggest mistake? - Lower nutrition level /less variety of food leading to more health problems/ smaller body builds. (according to archeological finds) - Risk of starvation as we depends on less and less variety of crops - Agriculture leads to crowding and vice versa which lead to the spread of spread of parasites and infectious disease
More importantly, agriculture allows the accumulation of food (impossible for hunter gatherers who have little or no stored food, and no concentrated food sources like farms), which then lead to class division: The appearance of a non food producing elite over the masses of disease-ridden people.
Also the inequality of sexes:
"Freed from the need to transport their babies during a nomadic existence, and under pressure to produce more hands to till the fields, farming women tended to have more frequent pregnancies than their hunter-gatherer counterparts-- with consequent drains on their health."
So why the heck did our ancestors choose agriculture over hunting gathering?
Because a hundred malnourished farmers can still outfight one healthy hunter.
Farming allows us to support more people, though with a lower quality of life. Our mistake was to choose farming over birth control. To most of us, the above argument seems ridiculous. However we belong to the elites: who are dependent on oil and minerals that must often be imported from countries with poorer health and nutrition.