Neil Tyson’s pick whiffs a little like American exceptionalism. IMO, Columbus etc. is way too late to be No 1. Things such as colonialism are built on a foundation, without which there is nothing.
Adopting fire is the biggest thing ever, if you ask me. It was the prerequisite for everything, from colonization to agri to metalwork to warfare to engines.
Fire was first mastered by a different species of hominid, not by our particular species.
Arguably, learning to use fire was the most important thing to happen to our genus. Ditto for flint knapping/tool making.
With the calculator. On the watch.
Do try to keep up!
We never should have left the oceans.
But they’re so tasty!
Possibly also true for language, come to think of it. We don’t know, and I don’t see how we’ll have a way to know.
I’d say the development of written language. Verbal communication and memory are good but they place a limit on the amount of information a society can hold and transmit. Once a society develops writing, it can store and thereby accumulate information.
This is a good point, the most significant thing might not have manifested itself yet. Ditto for AI. It might save us, it might doom us, hell, maybe we will never achieve it.
Not “but”, because. 
I think the Monolith teaching us how to murder each other with hand tools is significant. 
Alright, I’m going, I’m going.
There’s one thing. ONE THING that humans are really good at, and we can’t even take credit for THAT?
Different species? Have you seen my robust bone structure with the massave jaw and pronounced brow? Okay, that’s fair.
When I think of the most significant things to happen to us I’m thinking it terms of what changed us the most. I can point to how the development of agriculture changed us, but I’m not sure how the bottleneck 70,000 years ago changed us. Can anyone help me out with that? I’m not arguing the event isn’t a good candidate, I’m saying I don’t get it, but then a good friend once told me, “You were not put on this Earth to ‘get it,’ Odesio.”
More focused on inventions I remember reading a strong defense of sewing as the one of most impact.
It makes sense that sewing would be the common thread.
You’re just needling me.
We are just rebels without a clew.
I’d say that developing language is the most important, except that I think I’m also inclined to call the development of language the origin of our species, and so “thing that happened to the human species” has to be since then. So my next choice would be writing.
How about compound tool use? Albeit likely closely concurrent and related to language development.
The thing is, I’m not convinced either language or compound/complex tool use is unique to H. sapiens sapiens. I can’t prove it because I don’t have the science and research chops to do so, but I’m pretty sure H. neanderthalensis had both of those. It may have been different than the versions used by our species, but I think they did have them.
For “most significant for our particular species” I’d suggest candidates are agriculture and writing. Sure, the Age of Exploration with people like Columbus and the Columbian Exchange are also very important and I can see an argument for that. Also an argument for the Industrial Revolution and basing so much of our society’s energy on petroleum sources, and for computers and automation, but I think those candidates are much weaker at this point.
Wow, this kind of blows my mind, the idea that our species starts with development of an innovative rather than biology.
While possibly true, I’m not sure this is a disqualification. They aren’t necessarily mutually exclusive.
Swiss Army knives???