That day Mary looked tired; her eyes looked small for the first time(,) and her mouth contorted into a yawn every five minutes.
I'm confused because I found similar constructions on Google Books. Some of them have commas and others don't. Maybe the comma is optional in cases like these?
Punctuation is a matter of style, not grammar, so your first concern should be whether your sentence's punctuation helps or hinders the reader.
The comma asks the reader to pause in your second independent clause. The question that should be asked is: pause for what? Since the comma introduces a pause, the emphasis is placed on the final subordinate clause:
... and her mouth contorted into a yawn every five minutes.
If you wish to place a special emphasis on that clause, that is entirely up to you. But you have to be sure this is the effect you want.
Punctuation is an attempt to make text read the way speech sounds. Read your sentence aloud, giving the comma a pause and moving forward unhindered when you remove it. Which do you like better? Which conveys what you want that sentence to sound like? That is all that matters in that case, and, to answer your main question last, that particular comma is decidedly optional—the option being yours and yours alone.
And here's a lagniappe for you, about deciding whether or not to use a comma.
