Okay. I think Timmy has the right of it. Let's give it a shot.
Push the outbreak of Spanish Flu ahead to mid-late 1915 and have it make a lucky early jump to Europe so it's even less clear that it came out of Asia. Have both sides vaguely suspect (I'm thinking yellow journalism here) that the other had something to do with the virus.
Just as OTL, the plague kills as many as the entirety of the war. In OTL, though, the war was well on its way by the time it hit. In this one everyone is still adjusting to total war. The sudden loss of manpower slows down all the upcoming offensives and reduces immediate interest in secondary fronts. Ironically, Germany does well out of the outbreak. The blockade was not starving people yet, the population is healthier, and fewer die as a result. It will also increase the time it will take before the blockade starts really hurting as it lowers the population before stocks run low. All told that gives you the potential for a longer war.
Both Britain and Germany had biowarfare programs going during the war. Thanks to their suspicions, British intelligence digs a little deeper and finds the German one. From their fragmentary intelligence, the horror of the flu, and the jockeying of the UK biowar program for funding ("If you don't fund us, the Germans will kill us all!") they convince themselves the flu was German work. Masses of funding go to develop bioweapons and protect against them, and the French start their own program. The Germans find out about their enemies' programs and assume they created the flu.
Now the problem is, it's very hard to work out how to get from there to a civilization-destroying bioweapon. People are still vaccinated against smallpox, for example. Even harder is getting such a viscious weapon before the Great War comes to a halt from something else. We could argue about how long it could go, but let's save time and just cap it at 1921, tops. Revolution-related conflicts may go beyond that.
The most practical of the weapons they were working on was weaponized anthrax. It would have been used much like poison gas, and would have differed only in its ability to last longer and in the lag before the effects showed. Next most practical were a series of anti-livestock and anti-crop weapons.
You know, that might be enough.
Both sides hold off on using germ warfare at first, knowing how useless poison gas was in terms of winning a war. We'll handwave away the Zimmerman Telegram to put off American entry. When submarine warfare begins in earnest, the Germans combine it with biowar attacks on Britain's crops. It doesn't cause mass starvation, but it does wreak havoc and increase the dependency on imports. Naturally, the British reply in kind and more thoroughly. A few of the things (fungal, bacterial, viral) spread beyond the target countries.
At that point the neutral nations become suddenly wary of ships coming from Europe, and the conventional wisdom in America becomes "don't touch." This only increases as the Europeans keep up a slight tit-for-tat use of crop warfare, while holding the "big guns" in reserve. Biowarfare against humans is very rare and entirely on the Eastern Front.
Without American entry, the Michael Offensive isn't rushed, and nearly wins Germany the war right there. In desperation the French spread masses of anthrax dust in front of the German spearheads. It's not decisive, but that doesn't stop everyone thinking it so. The Germans leave their own anthrax contributions as they retreat from the offensive's more extreme salients. In 1919 the British begin mass bombings of the Rhineland cities (it was planned in OTL). The next Zeppelin raid on Greater London drops not bombs, but a liberal dusting of anthrax. It would be difficult to overstate how horrible that is. Naturally, the Entente fires right back.
By now every outbreak of anything is blamed on the opposing side, or on "the Europeans" in the rest of the world. Trade with the New World isn't cut off, but it does plummet dramatically. Even the Dominions and Japan are suddenly careful with any ship coming from Europe.
In Europe, Germany has done better than OTL, but it is still outmatched: The Bolsheviks are slowly gaining ground in the civil war. The Entente is on the back foot, but slowly gaining ground in the Balkans, Italy and France. They "have" the Ukraine but are getting very little use out of it (the same transportation issues of OTL).
In desperation they prepare a massive crop warfare attack on the main Entente crops, what they eat and what they feed their livestock. They plant heavily in easy things like potatos and the few crops they don't have a ready weapon against. Of course, the British have picked up on what they are planting and are ready to respond with a few blights against just that. Both sides are also working on what human diseases they think they can keep from getting back to them.
The attack is introduced by spies and what zeppelins can be snuck under the cover of weather. The Entente can see what is coming as soon as it starts, and while they can't stop it, it's easy enough to reply against those few crops the Germans have been promoting. The blights cross each other until everyone is hit equally. Edible wild plants are collected en masse and everyone starts eating the grass-fed livestock.
What follows is an extreme version of what happened to Germany in OTL. The armies are initially given what they need to keep up the fight, and the rest is divided between everyone else. Human diseases cut a swathe through the weakened civilian population. Revolutions topple nearly every government in Europe and more or less every the national minority go its own way. The remaining soldiers abandon the trenches and walk home. The UK ends up at war with Ireland over its sheep. Maybe Scotland, for that matter.
The New World quarantines itself as the blights and plagues sweep Eurasia and North Africa. Rice wouldn't be targeted, so most of Asia is relatively safe, but a lot of colonies will go their own way. Sub-Saharan Africa has a different crop base, and the famines there are due to local crops being sold in Europe.
It's not going to be a Stone Age Europe, per se. But closer to that than it would be to the Industrial Age. The crop warfare bit is extrapolating a lot from what we've seen in OTL and what I know of the science, but I think it's all doable.
Thoughts?