When Amy sees Sheldon obsessively tying and untying his bow tie the day before their wedding, Amy tells him it doesn't need to be even because sometimes a little asymmetry looks good. On the day of the wedding, Sheldon stops his mother from trying to straighten his bow tie, saying it's supposed to be a little asymmetrical. When Mary comments that sometimes it’s the imperfect stuff that makes things perfect, Sheldon has a flash of inspiration and rushes to see Amy. Sheldon and Amy’s wedding is delayed as they excitedly work on a new theory of “super asymmetry”.
In 2010, Leonard, Howard, and Raj mined a lot of Bitcoin, now worth thousands of dollars, but left Sheldon out due to his fear of tax implications. Flashbacks are shown of how the Bitcoin ended up on an old laptop of Leonard's, which Penny gave to her old boyfriend Zack after she and Leonard broke up. In 2017, Leonard and Penny retrieve the computer from Zack, who first shows them a video of a drunken Penny apologizing for breaking up with Leonard. The Bitcoin is not found on the laptop. Sheldon had moved it to a flash drive on Leonard's keychain to teach the guys a lesson, but Leonard lost the keychain years ago. A final flashback to 2013 shows Stuart discovering the flash drive, which he decides to erase and sell for $10.
Science has also interfered with the characters' romantic lives. Leslie breaks up with Leonard when he sides with Sheldon in his support for string theory rather than loop quantum gravity. When Leonard joins Sheldon, Raj, and Howard on a three-month Arctic research trip, it separates Leonard and Penny at a time when their relationship is budding. When Bernadette takes an interest in Leonard's work, it makes both Penny and Howard envious and results in Howard confronting Leonard, and Penny asking Sheldon to teach her physics. Sheldon and Amy also briefly end their relationship after an argument over which of their fields is superior.
Filming proceeds smoothly – makeup artists do touch-ups, a prop master replenishes the pickle supply – with humor and camaraderie between takes. When a reshoot is needed because Simon Helberg, who plays Howard, held his napkin in the wrong hand, Kaley Cuoco, who plays Penny, lifts her food box high and mockingly asks, “Does it go over my head? I don’t remember.”
In March 2017, CBS renewed the series for two additional seasons, bringing its total to twelve, and running through the 2018–19 television season. On August 22, 2018, CBS and Warner Bros. Television officially announced that the twelfth season would be the series' last. This stems from Jim Parsons' decision to leave the series at the end of the season if the show were to have been renewed for a thirteenth season. The series concluded with an hour-long finale consisting of two back-to-back episodes on May 16, 2019. A retrospective, hosted by Johnny Galecki and Kaley Cuoco, aired at 9:30 P.M. ET/PT, the night of the finale, following the season two finale of Young Sheldon.
After Sheldon reminds the guys about the time they mined Bitcoin without him, the guys go on a quest to find their suddenly valuable missing cryptocurrency. They realize the currency is on a laptop which Leonard gave to Penny when they dating, which she then gave to her ex-boyfriend Zack. After Leonard and Penny go to Zack's apartment, he shows them a seven-year-old video that Penny recorded on the laptop soon after she broke up with Leonard. Leonard is touched by the video which shows a drunk Penny lamenting the break-up of her relationship with him.