I'm trying to figure out what period of time in human history gives an influenza-like virus the best chance of exterminating 80% of human life within the span of no more than 2 years.

Basically, it should be at a time period where transportation technology is advanced enough and human population numbers are large enough to adequately spread the disease across the entire globe, while still being primitive enough such that medical technology will not be able to exterminate the disease.

This disease is similar to influenza: however, it has both airborne transmission and bodily fluid transmission, and an incubation period of 3 weeks instead of 2. Finally, this strain of the virus has an 80% lethality rate; much deadlier than regular influenza.

Other than these differences, the symptoms, once the incubation period is over, are identical to the influenza we are familiar with.

It is important to note that this scenario should take place only after humans have spread to every continent. So no scenarios wiping out the first humans in Africa before they've had a chance to spread to Australia and America.

Just after World War I would be the best time to wipe out humanity, and we even have a real 2-year-long deadly pandemic to base this on.

The Spanish Flu of 1918-1920 affected around 500 million people around the world, and caused 50-100 million deaths. Considering the world population hit 2 billion in 1927, a quarter to a third of the world experienced this pandemic over the course of just two years.

The reason the disease spread so far and so quick was due to the close quarters fighting of WWI, combined with massive post-war movements of troops and displaced civilians. Soldiers from across the world came to to the trenches, got infected with all manner of diseases, and then went back home to celebrations of cheering crowds, hand shakes, and spontaneous kissing.

So, just spread your extra-deadly and extra-infections disease around the trenches of Europe on a cold November morning in 1918, and watch the disease spread around the world as soldiers eagerly return home.

If you want to increase the chance of success, you better hit a weakened population.

Look at the Spanish flu, January 1918 – December 1920, which struck after WWI, in a time of increased poverty and malnutrition:

It infected 500 million people around the world, including people on remote Pacific islands and in the Arctic, and resulted in the deaths of 50 to 100 million (three to five percent of the world's population), making it one of the deadliest natural disasters in human history.

In 2007, analysis of medical journals from the period of the pandemic found that the viral infection itself was not more aggressive than any previous influenza, but that the special circumstances of the epidemic (malnourishment, overcrowded medical camps and hospitals, poor hygiene) promoted bacterial superinfection that killed most of the victims, typically after a somewhat prolonged death bed.

If you want to wipe out 80% of the world's population with a disease that has an 80% fatality rate, then every person on the planet (or close enough to round up to 100%) has to catch it within the designated time period.

Normally I'd agree with others who have written about the horrific flu epidemic of 1918. If you made that flu even worse than it already was, the death rate would have been far higher. And it already was quite high.

But if you're going to infect every person on the planet, you need to come forward in time where pretty much everyone travels "to town" regularly, most people visit medium to large cities at least a couple times a year, travel over a few hundred miles is also common, and international travel happens enough that everyone will meet a few people that have traveled internationally lately.

Perhaps the 1970's.

Anti-viral treatments weren't that great (they're not all that great now but they exist) but travel was common and most people owned cars. Flu vaccines were around in the 1930's but, even now, they're ineffective against any strain not directly included. If the companies making the shots are blindsided by this upcoming strain (which is likely), the shots won't help anyone.

What will get you is the effective and near instant communication of the 1970's. TV and radio. A lot of people will be saved from catching it by being warned. But this would be true in earlier times as well. In 1918 there were telegraphs and daily newspapers. A delay of one day (or maybe only 12 hours) in announcements won't make that much of a difference.

But if you (frame challenge) change the incubation period, you can achieve your goal. Make it 6 months, or even a year or two.

Look at something like AIDS. The very long incubation period (and initial lack of a diagnostic test during the incubation period) is what allowed it to spread as much as it has, even though HIV is really not very contagious (you need direct blood or sexual contact and even then transmission rates are low (the average risk of contracting HIV through sharing a needle one time with an HIV-positive drug user is 0.67%), plus it doesn't survive outside a host more than a few hours in almost all cases).

The 1970's works well here because you're still in the "free love" stage in the US and some other countries, AIDS hasn't hit yet so those skill sets aren't around, it's been a long time since the Spanish Flu, and epidemics like polio and smallpox are mostly gone, giving a false sense of security.

Replace HIV with your nasty-flu, with its high contagion rate, add in a long life outside of a host, and a very long incubation period, and you might just get your pandemic.

During WWII there had been a global mobilisation of personnel. If medical checks and basic prophylactic standards had not been in place, any flu-like disease could have easily resulted in a global pandemic.

During the slave trades, there have also been a massive human displacement across three continents. This facilitated the spreading of diseases. However, the speed of transportation made it nearly impossible for any disease to spread across the globe and wipe 80% of the population in two years.

However, the 1883 Krakatoa explosion sent volcanic dust all around the world. If your flu is caused by a pathogenic archaebacterium, then that could be your solution. The pathogen was diffused in the atmosphere as a result of the volcanic explosion, it would have survived because archaebacteria can survive such extreme events, and if they don't, their spores will. Rain and water vaporation can bring the correct aerosol in the range of human nostrils, and the time period, late XIX century guarantees the absence of medical infrastructure capable of tackling a worldwide pandemic.