"The Sign of Three" opens with Lestrade and Donovan unable to catch a criminal gang, Waters Gang, over a period of eighteen months. The opening scenes show Lestrade getting increasingly frustrated, with each passing month. When Lestrade is all set to catch the gang red-handed, he gets a text on his cell phone, "Help. Baker St. Now. Help Me. Please." Lestrade tells Donovan to go ahead and make the arrest, as he needs to go. A worried Lestrade calls for maximum back-up at Baker Street and drives-off in his car.

Lestrade runs-up to Sherlock's room only to find him in a thoughtful state, sitting in front of the laptop. "This hard, very hard. Hardest thing ever have to do." Sherlock has to write a best man speech and he needs anecdotes. Obviously, the maximum security is not needed.

Ms Hudson catches Sherlock practicing waltz for Watson and Mary's wedding. It is the big day, according to an excited Ms Hudson. The wedding of Watson and Mary is on the day. Sherlock does not share Ms Hudson's excitement and like his landlady, he does not think marriage changes people. Ms Hudson points out to him that he won't possibly understand that because he always lives alone.

Ms Hudson walks down her memory lane and talks about her chief bridesmaid at her wedding, and how they were supposed to be best friends forever, but they hardly saw each other after the wedding. She [Ms Hudson's friend] cried the whole day, saying that it is the end of an era.

Sherlock looks at his best-man dress and says: "into battle." The scene shifts to a mysterious man in uniform getting ready. He is using only one hand to do that.

Watson and Mary come out of the Church as a married couple. Sherlock is standing with them and the photographer asks him to move out of the picture as it is the newly-wed, couple picture. A bridesmaid tells Sherlock that he is going to be "incredibly useful." The incredibly useful means getting first impression information on the interesting looking men at the reception.

The mysterious man arrives at the wedding reception. He is the former commanding officer of Watson, Sholto. He is a good friend of Watson and holds the designation of Major. Sherlock wonders if they are good friends why Watson doesn't talk about him. Mary says that Watson talks about the Major all the time to her. Sherlock is surprised to know that Watson never shuts-up about the Major. Sherlock is jealous and Mary tells him that, "neither of us were the first."

Mycroft is working out and is not at the wedding. Sherlock calls him up and Mycroft tells him that the couple will be delighted to not see him on their wedding day. Mycroft tells Sherlock that it looks like he will be seeing him a lot just like the old time. Like Ms Hudson, he also mentions "end of an era" and adds it is the beginning of "John and Mary, domestic bliss." Sherlock calls it the "beginning of a new chapter." The call ends on Mycroft telling Sherlock, "enjoy not getting involved, Sherlock."

It is time for Sherlock's best-man speech. As expected, Sherlock gets the stage fright and is finding it difficult to continue after the initial two lines. Sitting in the audience, Lestrade remembers the day he and Molly had a conversation about Sherlock being the best-man and the worrying prospect of him giving the speech in front of so many people. The flashback shows a hysterically laughing Ms Hudson and Watson walking in, asking for Sherlock. Ms Hudson mentions telegram and in the present time, Watson gives the hint of telegram to his best-man. Sherlock gets the cue and starts reading the telegrams that have been sent to Watson and Mary, but soon gives-up. He mentions about the first time Watson had asked him to be his best-man.

In the flashback, Watson tells a clueless Sherlock that he needs a best-man for his wedding. Sherlock suggests other names, but Watson says that he wants the two people he loves and care about the most to be at his side on his big day. The first is Mary and the second person is Sherlock. A completely shocked Sherlock does the fluttering of eyes, and does not say anything for a long time.

The best-man speech may have begun with 'terrible' written across it, but then Sherlock soon says all the right things, including saying that Watson is sitting between two people who love him the most in this world [indicating Mary and Sherlock]. Also, he mentions about these two people have a life-time ahead to prove that. Everyone is touched by his speech. They are teary-eyed and Watson gets-up and envelops Sherlock in a tight hug.

Sherlock talks about his and Watson's association in solving cases. The bizarre murder cases that they had solved, together. He talks about two particular cases, the murder of a royal guard and the Mayfly Man.

The royal guard had emailed Sherlock about a man keeping a watch on him, all the time. The guard was murdered before Sherlock or Watson could have a talk with him. It is one of the unresolved murder cases, and at the reception, Sherlock asks for the one key element of the case. Neither Lestrade nor Molly's boyfriend are able to answer that, correctly. Sherlock says that there is only one element in the element and that is while he was busy solving the murder, Watson was trying to save the royal guard's life.

Sherlock also talks about another of their bizarre, unresolved case, 'The Mayfly Man'. Sherlock and Watson were completely sloshed when a woman had visited them. In their sober state of mind, the two would have dismissed her, quickly. The woman had talked about a ghost that she had dated. The man had disappeared after dating her and when she had visited his place, she had found that he had died a day before her date. Sherlock and Watson had visited the man's house but had landed up in a prison cell thanks to their drunken behaviour. Sherlock had gone through a blog on dating men from the spirit world. He had identified women who had similar stories to share. Sherlock could not find something that could link all the women. However, he had identified that they all had some secret. The Mayfly man had stolen the identity and house of the dead men mentioned in the obituary section.

As part of the best-man speech, Sherlock says that his and Watson adventure was full of mystery, murder and mayhem, and now there will be a new adventure for Watson and Mary, which is the beginning of a new chapter. However, he drops his toast drink when he suddenly realises that the woman who had come with her case of dating a ghost had mentioned Watson's full name, John Hamish Watson. Watson hates his middle name and only a handful of people knew his middle name, including Sherlock and Irene Adler. The only time he had made that name public was on his wedding invitation and that invitation card was sent to a limited number of people. Sherlock realises that Mayfly is there in the reception.

Mycroft's apparition in his head tells him that if a person assumes false identity, it suggests of criminal intention. Also, it is suggestive of intelligence and planning, while elaborate planning suggests murder. Sherlock walks around the reception hall, trying to figure out who will be murdered. He texts Lestrade to lock down the place.

Sherlock says to the invitees that "lets play a game. Lets play murder." He realises that Sholto will be murdered. Sherlock gives a slip to Sholto, telling him about that. He tells Watson to save Sholto. In his hotel-room, Sholto intends to kill himself. He tells Watson that that he will open the door only if Sherlock correctly tells how the royal guard was murdered.

Sherlock is able to finally crack that murder mystery. He tells Sholto that a dagger was put in the guard's tight belt, and it became lethal once the binding was removed. Sholto intends to die the same way. However, Sherlock tells him not do that, especially on Watson's wedding day. Sholto opens the door and Watson is there to help provide medical attention. The photographer is caught and is revealed as the Mayfly Man. The death of the guard was a practice run to kill Sholto.

Murder case solved and a life saved, Sherlock plays the violin while John and Mary dance. He says his final vow that he will be always there for Mary and Watson. He then says, "I'll always be there for all three of you." He has correctly deduced that Mary is pregnant. He tells the newly married couple that they have had enough practice and will make wonderful parents. Sherlock adds that they would hardly need him, now that they have a real baby.

The dancing begins. Everyone is happy and dancing. Sherlock sees that and quietly walks out of the wedding hall, probably realising it is the end of an era.