Stacey Dash was 29 when she played Cher’s best friend in the 1995 movie Clueless. She reprised the role during Clueless’ incarnation as a sitcom from 1996-99. The series finale was Cher and her friends’ high school graduation, which meant Ms. Dash was a 33 year old playing an 18 year old in 1999.
Gary Burghoff was 29 when he first started playing Radar O’Reilly on MASH. He played the role for eight seasons (Only two episodes in the eighth) and it was often remarked that he was too young to drink. (So under 21, or maybe that would have been 18 at the time?)
Jonathan Winters played an infant on Mork & Mindy. 
That was my understanding too. In fact, there was an early episode set during the 1956 Presidential Election in which Fonzie gave a short speech supporting the re-election of Ike. Given the voting age was 21 at that time, it could be implied that the Fonz at the time was of voting age (or, if not, somewhere between the ages of 18 to 21).
Of course, continuity and extreme detail didn’t really matter that much in that show.
Wikipedia says Fonz was 19 in 1956.
But Bart is still 10. Not a teen. 
Do movies count? There was an extended flashback in The Natural, where Robert Redford and Glenn Close had to pull it off even though they both had to be in their forties already. You almost couldn’t see them at all, through all the Vaseline on the lens.
I haven’t seen that movie in ages, and I don’t recall that scene. It sounds like Redford’s visage was obscured pretty well, though.
Not so with Tom Hanks, a sprightly **37-year old **when he played Forrest Gump as a high-schooler.
Leo Gorcey made Bowery Boys movies until 1956, when he was 39. They showed on TV all the time, so I think they count.
They weren’t. They’d been graduated from college for at least a year before Vanessa showed up on the show.
Crap. Still, she’s hawt!
At the final/graduation episode of Head of the Class, where since the kids were gifted presumably they were all 17-18, the actors included:
Brian Robbins (as Eric Mardian): 28
Tony O’Dell (as preppy Allan): 31
Dan Frischman (as nerd Arvid): 32
Michael De Lorenzo (as Alex): 32
The remaining cast was mostly early to mid 20s.
Erin Karpluk (31) portrays Erica Strange, in ‘Being Erica’. In each episode she goes back in time, sometimes to her teen years.
Check out post #18.
Richard Crenna played William Denton probably when he was in 30s. Depending on which birthdate one credits, he might have been anywhere between 29 and 35 while he played the wierd teen in Our Miss Brooks.
Keiko Agena who played Lane Kim on Gilmore Girls was 27 when she started on Gilmore Girls.
Taylor Kitsch who plays Tim Riggins was 25 when the Friday Night Lights TV series started. Scott Porter who plays Jason Street was 27 when it started. Minka Kelly (Lyla Garrity) was 26. Strangely there is a whole other crew who are ACTUAL high school age.
Susan May Pratt (Mandella) was 25 when 10 things I hate about you was released.
Jason Earles, who plays Miley Cyrus’ older brother in Hannah Montana, is 32 years old, just under 15 years younger than his TV father. I’m not sure if they ever mentioned how old he’s supposed to be in the show, but he acts as if he’s seven years old.
And I think I remember one episode where he filled in as a substitute teacher at the high school.
A movie example, but Moaning Myrtle from the Harry Potter series was a teenager when she died, and presumably shouldn’t have aged since, but was played by Shirley Henderson, born in 1965 (which would have made her 37 when she started the role).
Perhaps a more challenging thread would be one on TV shows where the teen characters really were played by actors roughly the same age as the character.
In the movie 18 Again! George Burns, then aged 92, sort of plays the role of a teenager. (The premise of the movie involves a body swap, of course).