The show doesn't get too technical into football, so a non-football fan shouldn't be lost while watching.
Here's a crash course on fantasy football that should be more than enough to get someone through the show:
1) The NFL has each team generally play once a week (there's 17 weeks in the season and 16 games, so each team gets one week off known as a "bye," which is sometimes a plot point in the show). 80% of the games are Sunday afternoon with a few games Thursday, Sunday, and/or Monday nights.
2) The league has a draft each year so that each NFL player can only be owned by one team in the league. The ones not drafted are considered "free agents" and any team can pick them up.
3) For those of you who know soccer, this may help you out: the goalkeeper generally plays the entire game and the backup goalie only goes in if the starter is pulled, injured, or ejected. Otherwise, the plan is to sit the backup on the bench the entire game. In NFL football this is basically what its life for every position; there's starters who are expected to play most or all of the game and backups who play little, if at all. Now, there's certain situations where teams put different players in for different plays but thats not relevant here. So a typical thing which happens in fantasy football (and does happen in the show) is a starting player gets hurt and fantasy players race to the computer to pick up a backup.
4) As you can probably guess, there are a few stats that players get positive points for and a select few they get negative points for, including fumbles, interceptions, missed field goals, or defenses giving up a lot of points.
5) There's a league schedule at the beginning of the year and each team has a different opponent each week. Whomever gets more points in each match wins the week. So at the end of week 1, half the teams have 1 win, 0 losses, the other half have 0 wins, 1 loss. Basically, at the end of every week, half the players are happy and the other half are not.
6) At the end of the regular season, a select few players make the playoffs. Playoffs are single-elimination each week; you lose, you're out! The last 2 teams left play for the championship.