Probably not exactly what you’re after, but I seem to recall the ST:TOS episode “Mudd’s Women” where someone asks McCoy a question and, distracted by the women, he replies “Yes… yes they are.”
Surely not the first, but there’s the Seinfeld episode in which George mistakes an onion for an apple.
Wow, it’s been a while! I would never have thought that was the B-plot from “Whacking Day”!
Holy crap. Please tell me you were a script assistant on that episode or something, before I start a new religion around you.
The first thing that came to mind was another Simpsons, in “Bart vs Australia” (February 1995)
Milhouse: Hey, Bart! The bakery caught fire and all of downtown smells like cookies! Wanna go smell?
Bart: Yes… Yes, I do.
Bzzzzt. He didn’t repeat the word “Yes.”
Is? Yes, yes it isn’t anything…that’s the beauty of it.
Nope. I was just an impressionable youngster, who was young enough to find hemorrhoids side-splittingly funny.
In retrospect, I probably had to ask my parents to explain it. They would have been hideously uncomfortable with that. Which probably made it that much funnier, and that much more memorable.
I must’ve been impressionable, too, because it is thanks to Sanford & Son that I can’t take the Teddy Roosevelt nickname “The Rough Rider” seriously, or drink sangria without thinking about doing a spit-take. 
Certainly an early progeniter of this trope has to be Kyle Machlachlan. The scene from the 1987 sci-fi flick “The Hidden” in which he confesses to his police detective partner that he is an intergalactic law enforcer was actually pretty famous at the time for his deadpan delivery. (I couldn’t find a single clip of this scene. The whole movie is on youtube though, and it is worth watching.)
And of course the same actor’s signature role as Agent Cooper on “Twin Peaks” really helped popularize the deadpan, blunt 'Yes it is" (or “No it isn’t”) response.
Not the first of course, but the one that sprang to my mind immediately was a commercial. I think for HBO.
Trendy-looking director with beard and black suit. Someone comments that he makes “movies” and he haughtily corrects them that he makes “features.”
Some more blah blah blah and then the end of the commercial, cue the smoking hot chick who comes up to director guy. In her best awestruck sexiness she asks him if he makes movies.
Without missing a beat, he replies. “Yes. Yes I do.”
(I’m curious if my memory of this commercial is anywhere close to accurate.)
Yep. I’ve never even tasted the stuff, but I thought of that scene just this morning when sangria was mentioned in today’s Sally Forth comic.
I love this as a running joke on Phineas & Ferb, although that’s probably the most recent incarnation:
“Aren’t you boys a little young to be building a nuclear reactor (or whatever)?”
“Yes. Yes, we are.”
The funniest version was two delivery guys bringing them building materials. One asks the usual question, and the other delivery guy rolls his eyes and says, “Yes. Yes, they are. Sorry Phineas, he’s new.”
I watched Tootsie over the weekend and I think there was a “Yes. Yes, it it is.” in there. I forget the context, though.
Yup, great movie. Don’t remember that line in it, though.