"We know better than anyone," she said to Anderson. "It's hard to do a pilot, let alone get picked up for a season, let alone keep going."
She gave a nod to the consistently funny writing by show's creator Chuck Lorre.
"They were the underdogs from day one, and people fell quickly in love with them and wanted them to win, wanted them to do well," she said.
Another thing that helps? The friendly chemistry between the cast is real. Added Cuoco, "We really like each other."
The dynamic between these otherwise geeky and socially awkward geniuses leaves the audience rooting for the characters, she added.
"They fell in love early on with these four guys and wanted them to get the girl, wanted them to get the job, and it made science kind of sexy," she said.
Even with the show's acclaim, Cuoco recognized the rarity of such prolonged success.
"Every single day, we're shocked when we look at ratings," Cuoco said. "We're shocked that the people still want to see us. We love being there and you know, I don't ever want it to end but you know how it is."
The interview will air in its entirety on Variety's "Actors on Actors" Season 6, presented by Shutterstock, which premieres June 13 on PBS SoCal.