What happens when hyperintelligent roommates Sheldon and Leonard meet Penny, a free-spirited beauty moving in next door, and realize they know next to nothing about life outside of the lab. Rounding out the crew are the smarmy Wolowitz, who thinks he's as sexy as he is brainy, and Koothrappali, who suffers from an inability to speak in the presence of a woman.
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.
Leonard gives an interview on public radio where he admits physics research might be at a dead end. The university is furious and, while trying to think of reasons to put in a retraction, he depresses Sheldon into thinking he might be right. Howard and Raj come over and end up just as depressed. Getting drunk with Penny, the men go to the grave of Richard Feynman and realize there is hope for physics as long as they believe in it. Leonard accidentally sends a drunken email to Human Resources. Meanwhile, Amy and Bernadette agree with each other to keep quiet about the success in their careers so as not to upset Sheldon and Howard. While bragging to each other, they end up arguing which of their fields is better.
Sheldon cannot find the perfect wedding date and begins talking in his sleep, adopting the persona of a laid-back person who goes with the flow. Amy and Penny believe that his subconscious mind is trying to tell him to be more relaxed; his attempt to be so while wearing flip-flops ends in disaster. He decides to leave all the wedding planning to Amy while he wears a Star Trek uniform underneath his tuxedo. Meanwhile, Raj and Stuart both become interested in Bernadette's new coworker Ruchi. While she likes them both as friends, she does not want a relationship with anyone.
Howard and Bernadette learn their second child will be a boy, leading Howard to doubt whether he can be a good father to a son. He and Sheldon go out in the desert to test launch a model rocket, but it explodes, causing him further doubt. On the way home, Howard does a good job coaching Sheldon to drive them home, for which Sheldon tells him he will be a good teacher to his son. Leonard's mother Beverly begins talking to Penny as a friend and confidant, troubling Leonard, especially when he learns that Beverly told Penny that she was proud of her, a level of praise she never bestowed upon Leonard himself. When Leonard confronts Beverly, he is touched when she says that of all of her children's spouses, Penny is the one by whom she is most impressed and that, for this, she is indeed proud of him. Meanwhile, Raj helps Bernadette turn baby girl clothes into boy ones.
Amy and Howard begin collaborating on a neuroprosthetics project, upsetting Sheldon and Raj, who feel they are not spending as much time with them. When they seek solace with an annoyed Bernadette, she exploits the situation to trick Sheldon into doing Howard's chores. Penny employs the approaches recommended in one of Bernadette's parenting books to deal with Sheldon with success, but Leonard believes she is coddling Sheldon too much. Sheldon and Raj resolve the issue of missing their significant others by spending time together.
Sheldon's childhood science show with Professor Proton 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 has somehow taken the role instead. Talking it over with Arthur in his dreams he is still upset his idol is 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 saying Penny is irresponsible. Halley ends up saying her first word by calling Penny "Mama."
Bert asks for Sheldon's help in a geology research project relating to dark matter. Sheldon secretly agrees, but is too embarrassed to admit he is working with rocks. Bert finds out about this and ends their partnership. After talking with Amy, Sheldon goes to apologize, only to find Leonard has taken his place. Meanwhile, Raj runs into Ruchi again and goes out with her, but she does not believe in romantic love. After Howard and Bernadette tell Raj that he can just have sex with Ruchi, he agrees to keep it casual.
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 other's 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 hires 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've most likely stolen from other people's projects as well. Ruchi is not happy about this and promptly dumps Raj.
In 2010, Leonard, Howard and Raj mined a lot of Bitcoin, worth thousands of dollars seven years later, but leave 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 them 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.
When Raj loses a job interview at a 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 talk 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.
Howard and Raj are still fighting so Howard dis-invites Raj to Halley's birthday party. However, when Howard's designated party planner Stuart pulls out at the last minute, Raj agrees to plan the party, which doesn't turn out too well due to Halley being asleep, Bernadette on bed rest and no people turning up. When Howard and Raj get into a shoving match in the party's bounce house, they end up letting out their frustrations with each other, but also having fun and reconciling. Leonard is depressed upon receiving his successful brother's Christmas card and attempts to make a list of what he and Penny accomplished this year, but doesn't come up with much. This prompts them to think about their plans for the future, so they decide to go on trips and achieve more out of life together before starting a family. Sheldon cooks Amy a Little House on the Prairie-themed birthday dinner, which gives them both food poisoning. They eventually recover enough to attend Halley's birthday party with the others, where they decide to have fun in the bouncy castle and then have sex in Howard and Bernadette's house.
To discover who would be most qualified to be best man and maid of honor at their wedding, Sheldon and Amy subject their friends to a series of secret experiments. Also, Penny reveals her true feelings about Amy.
When Sheldon kicks Amy out to work solo, she and Leonard bond during a series of science experiments. Also, Bert the geologist replaces Wolowitz in the band Footprints on the Moon, and Sheldon finds Penny a surprising source of scientific inspiration.
Koothrappali finds himself in the middle of domestic drama when he learns the woman he's dating, Nell, has a very upset husband, Oliver. Also, when Sheldon rents his old room back for a quiet place to work, he drives Leonard crazy by being a model tenant.
When Sheldon petitions Wil Wheaton to appear on the new Professor Proton show, Wil offers a role to Amy instead. Also, Penny gets angry when she thinks the female protagonist in Leonard's novel is based on her.
When Bernadette won't go into labor, all her friends try different tactics to get things started. Also, Wolowitz confronts Bernadette after Amy accidentally reveals she's already chosen their son's name.
Leonard jumps through hoops to help secure the perfect wedding venue for Sheldon and Amy. Also, Bernadette and Wolowitz have a hard time deciding who should stay at home with the kids and who should go back to work.
Penny gets the opportunity to host Bill Gates at work when his company wants to partner with her pharmaceutical company. Also, Leonard, Koothrappali and Wolowitz do everything in their power to meet him, while Sheldon thinks he is the victim of an April Fools prank.
When Leonard learns Sheldon is the president of the tenants association, he decides to run against him. Also, Bernadette encourages Wolowitz and Koothrappali to find the owner of a drone after they find it in the backyard.
Sheldon takes the guys to a cabin in the middle of nowhere to meet a reclusive scientist; Penny and Bernadette improvise Amy's bachelorette party.
Sheldon’s comic book store experiences changes when writer Neil Gaiman puts Stuart’s store on the map. Also, Koothrappali takes credit for Penny’s astronomical discovery, and friendships are threatened.
Sheldon goes to Vegas to win money for science. Also, Penny and Bernadette take Amy wedding dress shopping, but her terrible choice entangles them in a web of lies.
When Sheldon learns that his mother won’t attend his wedding unless he invites his brother, Georgie, he and Leonard travel to Texas to end a family feud. Also, the Wolowitz kids inadvertently infects Amy, Bernadette, Wolowitz and Koothrappali with pinkeye.