The .25-20 Winchester, or WCF (Winchester center fire) was developed around 1895 for the Winchester Model 1892 lever action rifle. It was based on necking down the .32-20 Winchester. In the early 20th century, it was a popular small game and varmint round, developing around 1,460 ft/s with 86-grain bullets.

While the SAAMI pressure rating is a full 28,000 CUP, modern ammunition is often loaded lighter in deference to the weaker steels used on many of the original guns. The early black powder cartridges were loaded to about 20,000 psi, but the SAAMI rating is close to that of the high velocity smokeless rounds produced later. The high velocity loadings developed 1,732 ft/s.

It was easy and economical to reload, and was once a favorite with farmers, ranchers, pot hunters and trappers. Though the .25-20 has been used on deer and even claimed the James Jordan Buck, a whitetail deer of long standing record in 1914, it is now rarely used on large-bodied game due to its sedate ballistics and light bullet construction, which make humane one-shot kills unlikely.

The 25-20 Winchester should not be confused with the similarly named .25-20 Single Shot; the two cartridges are markedly different and will not interchange with one another.