Reddit reviews Sports Illustrated Blood, Sweat and Chalk: The Ultimate Football Playbook: How the Great Coaches Built Today's Game

That's one of the contributing factors of Football IQ, and the very basics. Other than that, you have to know what defender is going to do what in which system.
There are QBs who also determine blocking schemes for their line. They say which blocking scheme to apply for which play, and switch them up if need be.
Very, very basically, a spread offense spreads out the defense across the width of the field, instead of bunching everything together around the ball. If you spread the defense out, there are bound to be more holes. That could mean putting 4 or even 5 WRs out away from the Oline (hence, wide), for instance.
A lot of the times, they add in the read option in that play. If a certain defender goes into coverage or for the HB, the QB keeps the ball and runs through the gaps of the defense. If the defender stands pat, the QB hands it off to the HB (or throws).
There are some great books that explain a lot of these things. A few I would definitely recommend are (in order of how deep they go into stuff):

• Take Your Eye Off the Ball
  
• The Essential Smart Football
  
• Blood, Sweat and Chalk, which is slightly more advanced but the best out of the three. It dives into the history of the game. Absolutely fascinating!
  
  And Arians' book, The Quarterback Whisperer goes into the practicallities of making the jump from college to the pro's. It's a marvellous read!
  
  Edit: formatting
  

Read the book "Blood, Sweat and Chalk", you will have more knowledge than any two lifelong NFL fans you know afterwards.

reddit.com/r/footballstrategy/wiki

The Games that Changed the Game

Take your eyes off the ball

Blood Sweat and Chalk

are all great if you want to get into detail