Albert Barnes Commentary Isaiah 66:16

"For by fire will Jehovah execute judgment, and by his sword, upon all flesh; and the slain of Jehovah shall be many." — Isaiah 66:16 (ASV)

For by fire and by his sword - The sword is an instrument by which punishment is executed (see the notes on Isaiah 34:5).

Will he plead with all flesh - Or rather, he will judge (נשׁפט nı̂sh^ephaṭ); that is, he will execute his purposes of vengeance on all the human race. Of course, only that part is intended which ought to be subject to punishment; that is, all his foes.

And the slain of the Lord shall be many - The number of those who will be consigned to woe will be immense. However, in the culmination of the great drama at the close of the world, there is reason to hope that a large proportion of the human race, taken as a whole, will be saved.

For past generations, indeed, there is no just ground for such hope; for the present generation, there is no such prospect.

But brighter and happier times are to come. The true religion is to spread over all the world and prevail for a long period. The hope is that during that long period, the multitude of true converts will be so great that the total number of those who are lost, compared with those who are saved, will be much smaller than is commonly supposed.

Still, the aggregate of those who are lost, the slain of the Lord, will be vast.

I regard this description as referring to the coming of the Lord to judgment (compare to 2 Thessalonians 1:8).

Or, if it refers to any other manifestation of Yahweh for judgment, such as the destruction of Jerusalem by the Romans, it bears a strong resemblance to the final judgment.

And, like the description of that event by the Savior (Matthew 24), its language naturally suggests, and is applicable to, the final judgment of mankind.