Professor Proton, Sheldon's favorite childhood show, is being rebooted. After unsuccessfully auditioning for the part, he goes to Wil Wheaton for acting tips for his second audition. However, Sheldon is later dismayed when Wil is offered the role instead. Talking it over with Arthur in his dreams, he is still upset to see his idol replaced and considers Wil an enemy again. Meanwhile, Howard gets a vasectomy while Bernadette is on bed rest. Penny offers to take care of Halley for them, but they insult her by expecting her to be irresponsible. Halley ends up saying her first word by calling Penny "Mama."
As the theme of the show revolves around science, many distinguished and high-profile scientists have appeared as guest stars on the show. Famous astrophysicist and Nobel laureate George Smoot had a cameo appearance in the second season. Theoretical physicist Brian Greene appeared in the fourth season, as well as astrophysicist, science populizer, and physics outreach specialist Neil deGrasse Tyson, who also appeared in the twelfth season.
Amy enthusiastically accepts Sheldon's marriage proposal. However, when dining with Amy's colleagues later that night, Sheldon is offended that they are more impressed with Amy's work than his own. With help from Stephen Hawking, Sheldon later comes to grips with the fact that he will not always be the center of attention in the marriage. Bernadette is shocked to realize that she is pregnant again. She and Howard are not thrilled at the idea of having another baby so soon after their first. They attempt to convince Leonard and Penny to have a child as well, but are rebuffed.
After learning Sheldon went behind their backs to work with the military again, Leonard and Howard say Sheldon is like Thomas Edison, taking credit for others' ideas, while they are more like Nikola Tesla. Leonard and Howard bring in Barry Kripke to help create a better idea than Sheldon's, but Kripke goes to the military himself, cutting all three of them out. Meanwhile, Bernadette fears Ruchi is trying to steal her projects at work while she is on maternity leave and enlists Raj to spy on her. Though he finds proof that Ruchi may be stealing from Bernadette, Raj tries to defend Ruchi like a boyfriend would, pointing out Bernadette's hypocrisy as she would most likely have stolen from other people's projects as well. Ruchi is not happy about this and promptly dumps Raj.
According to Steve Holland who is the show-runner starting with this season, Wil Wheaton will return in this season since his absence from Season 10. And this has confirmed to be true since it has been stated that he reappeared in "The Proton Regeneration" (S11E6), along with Professor Proton, their first appearances since "The Opening Night Excitation" (S9E11) and "The Celebration Experimentation", respectively and a span of 43 episodes and a span of 37 episodes, respectively. Wil also returned in the 15th episode. Wil will also return for Sheldon and Amy's Wedding.
When Raj misses out on a job at the planetarium, his father says he has no confidence because Howard always makes fun of him. Raj distances himself from Howard and later gets the job. Howard is hurt by this (even after apologizing to him) and tries to make amends with Raj after his first performance at the planetarium but, when he sees him get a date, he leaves without speaking to him, thinking that the latter's life is better without him. Meanwhile, Sheldon and Amy try randomly dividing up wedding tasks, but they keep arguing. The only thing they can agree on is to get married, so they decide to just get married at City Hall. However, Sheldon decides that he wants a first dance with his new wife and they go home to plan their wedding.