You pick players in a multi round draft, usually snaking (the order of picks is reversed for each round), targeting a specific number of players from each position. Such as:
1 QB
2 RB
3 WR
1 TE
1 DF
1 K
Bench:
1 QB
2 RB
2 WR
1 TE
1 DF
1 K
Then, during each week of NFL games, you track your players performance to determine a score.
In some fantasy leagues you are competing head to head versus an opponent on a weekly basis, and in others it is just about who can score the most points in a given week.
If you have never played, it is a good way to learn more in detail about NFL Football.