Will I be able to play my vanilla save if I start a new one with mods?

There is an option to choose mods once you already have a save from the load menu. But, there isn't an option to do so on new save creation and these mods need to be on for world first creation and load with the game start up. So, if I have these on, will I have to disable them when I want to play a vanilla save (same build).