Knockout League was built by Grab Games specifically for VR rather than ported from another platform, and it wears its inspiration proudly: this is, in the words of one Metacritic reviewer, "about as direct a translation of the classic Punch-Out!! arcade-style gameplay as you're going to find and it absolutely works, even if it lacks some originality." The game even jokes about the first opponent not having a glass jaw — a knowing nod to its source material.

Gameplay is entirely physical: throw straights, hooks, and uppercuts based on your actual motion, block by raising your hands, and dodge by leaning or ducking. There are no button presses involved in the core fighting loop. Critically, the game is played standing in one spot — you don't move around the ring — which makes it one of the more compact-footprint boxing titles available, suitable for spaces too tight for the room-scale movement that Thrill of the Fight or True Boxing VR demand.