In a knock-out tournament (a tournament in which the winner of any match moves to the next round and the loser gets eliminated), there are 22 participants. What is the total number of matches that must be played to determine a single winner?

In any pure knock-out tournament, every single match results in exactly one participant getting eliminated.
To find a single overall champion from a pool of $N$ participants, we must eliminate exactly $N-1$ participants. Because each elimination requires precisely one match, the total number of matches required is always given by the direct formula:

$$\text{Total Matches}=N-1$$

Given $N=22$:

$$\text{Total Matches}=22-1=21$$

This result remains fixed and completely independent of how the brackets, rounds, or fixtures are structured or seeded.