The very simplest form of layout would be a single column or block of content that would squeeze to any width.
Though you have already stated a preference for multi column layouts. Yes, you can squeeze the columns so far, until they get uncomfortable, then you will have to stack them. There is the option to hide secondary content in rollouts. We have already been through all this in another thread.
There are a number of methods for handling grid/column layouts:
There are Floats, an old method, not strictly a grid/column layout, but puts things on one side. Then when things get tight, media query, float: none; you can then make it width: 100%; or margin: 0 auto; to centre it.
display: table; can give you a grid or column layout, emulating a html table, but maintaining good semantics in your html by not using <table> tags where it is inappropriate. You can alter this layout for smaller screens by switching to other display modes, the possibilities are too many to mention.
There is Flex box, which is fairly new and very powerful, again the possibilities of what you can do are more than I have patience to write. But it allows you to switch between row and columns and re-order the flow.
I also read about something called Grid, which is a bit like fexbox and quite new. It is not at present well supported, so I would hold back on that for now.
Another one for columns is css columns. Different in that the columns are not separate elements, but a continuous block that flows from one column to the next, rather like newspaper columns. For responsiveness, you can explicitly sate, for example, 3 cols, the have a media query stating 2 cols, then for the smallest screens another stating 1 col. Or you can set a column width, and it works it out for you.
There may be other methods, but I can’t think of any right now.