Hoo boy.

So gotta clear up a few things about the war and historiography. Firstly I'll throw the "inevitable given their natural disadvantages" line right out. I find (and I'm sure most of this sub would agree) that these lines of thinking (IE in terms of inevitability) are determinations that are only ever comfortably made with the benefit of hindsight and are not actually reflective of the period itself. Of course there was a possibility that the Central Powers could have won, but they didn't and the reasons for that are many and not, I feel, easily chalked up to one primary factor. Rather a wide range of related factors that compiled on top of one another.

For starters: resources. The total war of WWI meant that intense amounts of economic might had to be brought to bear in order to fuel the war machine. While the industrial output of Germany was probably the strongest in Europe the same could not be said for the Ottomans, Bulgaria, or to a lesser extent: Austria-Hungary. The war very quickly shifted from a war of maneuver in the West to a war of attrition. Without the benefit of a vast colonial empire it would be difficult for Germany to sustain itself against the Entente in a war of attrition (to be clear, Germany had many colonies but was unable/unwilling to risk its navy to protect them, still nowhere near the amount of resources as the UK and France though). Moreover, the dependence on agriculture and the interruption to the agricultural production chain that this sudden mobilization caused meant that food would become an increasing concern for your average German. In the long-term Germany would not have been able to hold out in a siege-like war compared to the resources of the UK and France (and eventually too the USA). So their strategy had to be one of swift offensives and decisive victories which would bring the opposition to peace-talks. Also they would seek to mitigate the resource advantage posed by international empires in the form of submarine warfare, hoping to interrupt shipping enough to grind down their enemies through attrition even worse than they themselves were facing. Obviously these did not fully succeed in the long-term.

Secondly: Military and political mistakes. While the German army on the whole performed quite well during the war they were not the perfect war machine they were often portrayed as. Ultimately the British, the French, and yes even the Russians would learn and adapt and prove adept foes for them, despite many bungles that we frankly don't have time for in this question. Germany's allies were quite infamously did not perform particularly well during the war and as time dragged on would be more and more reliant on German armament and assistance to maintain their respective theaters of war (For example: Austria-Hungary was unable to defeat Serbia, a much smaller country than it, for almost a year and even then it needed help from Bulgaria and Germany). The Ottomans suffered from a horribly divided and separatist empire but militarily performed decently well, considering the circumstances. Politically Germany isolated itself majorly by attacking through Belgium which was intended to bring a swift defeat of France that obviously never happened. Making the invasion of Belgium both a political and military mistake. The Central Powers were able to knock the Russians out of the war but this came at a heavy cost and came too late, the US was already well on their way to having a military presence in Europe.

Thirdly: I don't want to oversell their role but the entry of the US did have a pretty decisive role in it too. While the central powers were in a sorry, sorry state at the beginning of 1918 and on the brink of collapse (three years of the most intense war the world has ever seen did a number on most countries). But they did decisively throw the Russians out of the war and gain a lot of (devastated) territory. Moreover the other allied powers were themselves were also quite exhausted and in a similarly sorry state of affairs. The Spring offensive of 1918 was effectively a last ditch effort to squash the Entente in Europe and (most likely) end the war in a German victory. Germany expended the last of its resources and planning on a hail-mary offensive hoping to win the war. While the offensive was initially successful it did not end the war and left the Germans (and the UK and France) gasping for breath. Meanwhile fresh US troops were entering the theater in growing numbers at a very crucial time. Though pretty much every European power involved was almost totally exhausted, the relatively unscathed USA, with it's massive industry and capability for a large army. After the first US involved offensive (the 100 days offensive) the German army all but collapsed. Meanwhile the southern Balkans and the middle eastern theaters were experiencing similar pushbacks. Facing economic devastation, restless civilian populations, and a self-apparent inability to maintain a coherent frontline. The countries of the Central Powers saw the writing on the wall and sued for peace.

So in short: Economic limitations coupled with poor military/political decisions + performance, and the entry of a fresh and massive country into the war lead to the Central Powers decisive defeat. However we should not view this defeat as an inevitability because frankly, there were several points in which they very well could have won the war had things gone a little differently.