Yes. The comma should be there.
Let's look at the wider context around that quote:
We used to trust in God. I think it was in 1863 that some genius suggested that it be put upon the gold and silver coins which circulated among the rich. They didn't put it on the nickels and coppers because they didn't think the poor folks had any trust in God. [...]
The President ordered the removal of that motto from the coin, and I thought that it was well. I thought that overstatement should not stay there. But I think it would better read, "Within certain judicious limitations we trust in God," and if there isn't enough room on the coin for this, why, enlarge the coin.
Source: Delphi Complete Works of Mark Twain, Google Books
Twain is saying that he doesn't think "We trust in God" should be on the coins, but he does think the longer, more nuanced version should be. Suggesting they enlarge the coin to fit this quote on would make sense with the rest of the sentence.
If he was asking the rhetorical question "why enlarge the coin?", this would go against his own suggestion in the previous clause. In this case, it would make more sense to link the two together by a "but" instead of an "and".
When the quote is reproduced without the comma after "why", it seems to be generally by less reliable sources. For instance, TwainQuotes.com (a website over which presumably less care has been taken than over a printed and published volume of collected works of Twain) has:
If I remember rightly, the President required or ordered the romoval of that sentence from the coins. Well, I didn't see that the statement ought to remain there. It wasn't true. But I think it would better read, "Within certain judicious limitations we trust in God," and if there isn't enough room on the coin for this, why enlarge the coin.
Note that even in this rendition, there is no question mark at the end. If the meaning was "why enlarge the coin?", then there should certainly be a question mark. If the meaning was "why, enlarge the coin!", then it could do perfectly well with just a full stop instead of an exclamation mark.
To summarise: the surrounding context, meaning, word choice, and punctuation suggest that "why, enlarge the coin" is the correct interpretation; furthermore, the sources which have "why enlarge the coin" tend to be less reliable.