She regretted her college choice almost immediately.
"I hadn't visited, never been to Pennsylvania before, but the campus looked wonderful in the catalog," Luddington says. "I was a city girl in the middle of an Amish town. It was quite a culture shock."
She transferred to the New York Film Academy in Manhattan after six months.
Now, 10 years after her visit to Hershey, she admits there are a few words that continue to thwart her, like anytime (which she pronounces like a Glaswegian dockworker) and O.R., a common abbreviation in the Grey's patois, but one that still lingers far too long in Luddington's throat.
Otherwise it's smooth sailing, which is fortunate because Jo has enough on her chart without worrying about how she sounds.
In Thursday night's episode, "Two Against One", the young doctor foolishly tries - in the O.R., as it happens - to resolve the toxic tension between Dr. Bailey (Chandra Wilson) and the recently returned Ben (Jason George).
This while she's still trying to repair her own relationship with Alex (Justin Chambers), which ruptured when she pushed him a little too hard to reconcile with his shady father ( Dexter's James Remar.)
"She's learning painfully that Alex is not happy," says Luddington. "It's not something that will go away."
For the actress, it's been a twisty road that has led her to Grey Sloan Memorial.
After graduating from the Film Academy, she moved back home for a time to fund her planned conquest of Hollywood. But her unsuitability as a waitress was evident even at a small pub in Crowthorne.
"My father came in and actually complained to the manager about me," she says, laughing.
Her big breakthrough came when she was cast as the lead in Lifetime's royal romance William & Kate in 2011.
"I think every British brunette girl in L.A. went to those auditions," she says. "Playing Kate Middleton was super-intimidating. I didn't imagine it would attract so much attention. Suddenly, we were being tracked by the British press while filming.
"They followed me to where I was living," says Luddington, 29. "I answered the doors in my PJs drinking my morning coffee and it was the paparazzi."
Produced and designed for American audiences, the film was not well received in Britain, as the actress found out when she went over there to promote it.
The Guardian called it "toe-curlingly, teeth-furringly, pillow-bitingly ghastly." Ouch!
"We don't have Lifetime in England," Luddington says. "They thought it would be a very serious piece. They don't understand the cheesy, guilty-pleasure aspect of Lifetime movies."
Just days after returning from that press junket, she started on Showtime's Californication as the naughty nanny Lizzie.
"I liked going from Lifetime to Showtime," she says. "I thought it was cheeky."
Auditioning for a part on Gilded Lilys, a failed pilot from Grey's creator Shonda Rhimes, led to her current role.
Luddington talks about the evolution of her character Jo for a minute before abruptly remembering her most formative American influences.
" The Wonder Years was one of the first shows I started watching as a kid," she says. "I wanted to be Winnie Cooper. I loved that show.
"And I was a huge Dawson's Creek fan, bordering on the tragic when I was 13, 14. All that teen angst."
So was she on Team Dawson or Team Pacey?
"Pacey," she says without hesitation. "I have a girlfriend, we still get into arguments with who [Joey] should have ended up with. Seriously. We still fight over it."
Seeing as how L.A. is a company town, has she ever run into Joshua Jackson, who played Pacey (more recently seen on Fringe)?
"I honestly hope I never run into him," she says. "I would be an embarrassing mess and confess my love for him."
But with an impeccable American accent.
9 p.m. Thursdays on 6ABC