I find it interesting that everyone in this thread is waxing romantic about the glorious 7x57, which, truly, is a good round, but yet that round has always had next to no popular acceptance in the US, except for maybe a relative few sporterized Mausers made from Span-am war booty in the first decade of the 20th century. Further, I bet no more than one or two posters in the thread actually own or regularly shoot a rifle chambered in the cartridge, so it’s a bit hard to take seriously the claims of its miraculous and still-totally-relevant ballistics. It’s a good round, in the same way that .30-06 is good, but neither are truly groundbreaking in and of themselves. The 7x57 has a lot of myths attached to it from Spanish American war experience, which arguably has more to do with postwar politics and possibly the military deficiencies of the non-clip-loading Krag-Jorgensen rifle, than any serious ballistic advantages of 7x57 Mauser.
The .30-40 Krag adopted in 1892 was the USA’s first smokeless military round. The 7x57 Mauser was designed and adopted around the same time. (Both were preceded by the 8mm Mauser, the .308 7.5x55 Swiss bullet, which has a claim to be the first true .30cal round, and even the Russian 7.62x54R adopted in 1891.) The .30-30 was our first commercial-market smokeless round, in 1894. The latter did a great deal to popularize smokeless powder for the general public.
The 8x57 revamped for Spitzer bullets in the early years of the 20th century (1903) forced the US (and everyone else) to do the same thing. It supplied the name of the pointed bullet. But even though it got the press, the 8x50R Lebel Balle D of 1898 was the “first” adopted.
One round nobody has mentioned yet is the venerable .43 Spanish Reformado chambering, which both increased the ballistic efficiency of the .43 Spanish black powder round, and was the first bullet to use a jacket (of brass) instead of just plain lead or a paper patch.
So, if we’re talking technical features that were groundbreaking, we’d have to pick from the 8x50 Lebel (1886, first smokeless) .43 Reformado (1889, jacketed) or possibly the Patrone 88 of the Gew 88 “Commission Rifle,” which used an 8mm projectile and was also allegedly jacketed in its first form, the 7.5x55 (1889, paper patched .308 size) or the 8x50R Lebel or 8x57S Mauser (spitzer.) Between these cartridges, the modern small bore, smokeless, ballistically-efficient cartridge came to be. Arguably, the cartridge that really summed up all these developments and went on to worldwide usage, both sporting and military, was the US .30-06, adopted in 1906. This cartridge also has the distinction of being chambered in the first generally issued and successful rifle caliber semi-automatic battle rifle, the Garand.
All in all, a tough question to answer decisively.