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I have two divs lined next to each other using the following CSS:

.overlay 
 display: flex;
 flex-wrap: wrap; 


.mainContent 
 flex-grow: 1;
 flex-basis: auto;
 margin: 5px;


.interactions 
 flex-basis: auto;
 flex-grow: 1;
 max-width: 400px;
 margin: 5px; 

When the width of the screen gets too small (i.e. .interactions can no longer fit) a new row is created in which interactions are placed.

What I'd like to do when that happens is for interactions to switch to max-width: 100%, is there any way to do this without using javascript?

There's two situations here

screen gets too small

1. if screen goes below 400px we're okay with the rules so far




2. if screen is above 400px but still too small, we end up with conflicting max-widths

is there anyway to do this without using javascript?

It can be achieved with media queries

@media only screen and (max-width: 600px) 
 .instructions min-width: 100% 

maybe you should use media queries?

@media (max-width: 400px) 
 .interactions 
 max-width: 100%;
 

you shuld to use the nowrap property,
the flex-wrap: wrap create new line when the intenrnal divs are too little, the nowrap not create, the code to remain in the same line is

.overlay 
 display: flex;
 flex-wrap: nowrap;

 
 .mainContent 
 flex-grow: 1;
 flex-basis: auto;
 margin: 5px;
 

 .interactions 
 flex-basis: auto;
 flex-grow: 1;
 max-width: 400px;
 margin: 5px; 
 

you can find the documentation here https://www.w3schools.com/cssref/css3_pr_flex-wrap.asp

Also you can find other details of the usage and the browser compatibility here https://caniuse.com/#search=flex-wrap

Using media queries is a challenge here because the breakpoint at which the problem occurs is dependent on the size of the flexible width .mainContent

So a better approach would be to have a min-width on .mainContent and use a media query for the breakpoint which is a sum of the min-width of .mainContent and max-width of .interactions + margins

.overlay 
 display: flex;
 flex-wrap: wrap;
 justify-content:stretch;

.mainContent 
 flex-grow: 1;
 flex-basis: auto;
 min-width:400px;
 margin: 5px;

.interactions 
 flex-basis: auto;
 flex-grow: 1;
 max-width:400px;
 margin: 5px; 

@media only screen and (max-width: 840px)
 .mainContent, .interactions
 max-width:none;
 min-width:none;
 

See it in action here: https://jsfiddle.net/gnu12Lfs/