* Gin's speech about "carrying a heavy weight on a long journey" in chapter 13 can definitely induce ManlyTears.
* The Inugami Arc.
* Early on in the series, Sougo asks the Yorozuya to investigate the illegal underground fighting ring, the top fighter of which turns out to be a kindhearted father to orphaned children who wants to try and start a new life. Just as he sets out to escape Edo and start over, the Tendoshu (who are behind the ring) have him killed. The following scenes with his last words and the children tearfully asking Gintoki to help them in exchange for their treasures (read children's trinkets) is touching in a heartwrending way.
* Episode 31, when Gintoki [[spoiler: gets amnesia from a traffic accident]]. Any attempts to help him fail. At the end, Yorozuya is destroyed by an incoming spaceship (Gintoki claims it's impossible for a human to stop it). Gintoki then tells Shinpachi and Kagura, more or less, "The Gintoki you knew isn't here anymore", and then leaves. Thankfully, he [[spoiler: regains his memories]] by the next episode.
* Tama's HeroicSacrifice at the end of her arc.
* Another early one occurs in episode 73 about a man and a bear cub he raised, only for him to be forced to kill it later when it becomes infected by a disease and goes rampaging in a mad fit.
* Mitsuba's arc in general, but especially [[spoiler:her death, with the normally sadistic {{Jerkass}} Sougo beside her bed, desperately clutching her hand and holding it to his cheek as she dies.]]
* [[spoiler:Ito's death]] at the end of Shinsengumi Rebellion Arc.
* At the end of episode 108, a short story about an orphan, Kyojiro, taken in by a group of Yakuza, he dies by the grave of the leader who he considered a father, believing until just before the end that he had failed to protect the people important to him. Of course, as soon as Gin-chan manages to convince him otherwise, he is fatally shot.
* Seemingly subverted then played straight in episode 130. [[spoiler:It starts out seeming like a slice of life story about an old dog and old man loyally dying at the same time, except the dog turns out to be an alien that eats planet and the old man was rude and told people to go die all the time. It's played straight in the end when it turns out that both don't want to die before the other because they don't want to make the other sad by leaving them alone and competing with each other while telling the other to die in the only way they can really show affection to each other. The old man dies as soon as he sees his last friend, the dog, die first after their race (while both are dying) so that he won't be left alone.]]
* Danzo Tobita AKA [[spoiler:[[ArcVillain Jiraia]]]]'s backstory as revealed at the end of the Red Spider Arc.
* The Four Devas Arc feature one in the form of [[spoiler:Otose's supposed death at the hands of Jirocho in front of her husband's grave. It's heart-wrenching.]]
** The moments leading up to the end were terrible too. [[spoiler: Otose gets Kagura, Shinpachi, Tama, and Catherine out of harm's way by telling them she's taking them out to eat. She tells them to go ahead before [[FaceDeathWithDignity turning around to go to the graveyard and meet Jirocho]].]]
--> [[spoiler: '''Otose:''' I have a favor to ask. They call me one of the Four Devas, but I don't have any members in my faction. My life is all you need. They serve no use at all. [[TrueCompanions They just happen to be my family.]]]]
** [[spoiler: Five minutes later, we see Gintoki desperately trying to get to Otose in time--[[YouAreTooLate but it seems he doesn't.]] Cue Gintoki unleashing his rage on Jirocho, only for him to lose and crawl desperately towards the dying Otose, accompanied by flashbacks of their first meeting and his promise to protect her.]]
--> [[spoiler: '''Jirocho:''' ''Get lost, watchdog. There's nothing for you to protect here.'']]
** The reunion of [[spoiler:Jirocho and Pirako]], damn you Gintama.
* At the end of episode 226, when the old prisoner [[spoiler:revealed that he knew the letters he was receiving were all written by]] the prison warden, his "[[spoiler:nasty but dedicated son]]".
* The end of the Renho Arc, which was filled to the brim with about as many shout-outs and parodies as ever, takes a sharp turn hard enough to induce severe MoodWhiplash and seemingly ends in one of these when Elizabeth left the series for good, [[spoiler:only for it to be ultimately subverted when it's revealed that the Elizabeth leaving is a temp, and the real Elizabeth was only on vacation. NEVER FORGET THAT SORACHI IS A TROLL OF THE HIGHEST DEGREE.]]
* In the Kintama Arc, our protagonist sudden returns to the Yorozuya after a drinking night, and he goes and salute their comrades, he finds out that he has been replaced by someone who is better than him, and the guys he thought to be his friends donít EVEN remember him. Itís not a joke. They arenít the only ones to have forgotten his own existence. And he just wants to beat the hell out of him to know a reason of why everyone forgot about him and he is just... there, taking the credit of everything he has done (over the past 40+ volumes/250+ episodes) but those who were his friends tell him that he is nuts, and that he just have to keep out of Kabukicho. Just dammit, seeing his face as Shinpachi and Kagura tell him that he CAN'T be acting that friendly on them is heartbreaking.
** Oh, and it goes downhill from there. Kintoki [[spoiler: convinces Gin that everything he lived is a lie, just his own invention... puts in doubt everything about him!]] It's painful!
** But I must say that someone cannot cry when after [[spoiler:[[DespairEventHorizon losing all hope of his own existence]], Sadaharu and Tama comes to his rescue, the robot maid tells him that he doesn't really have to lose his own light because it's what is differs him with Kintoki... and that he is the only one that must try to recover the memories of him with his friends]].
* The Courtesan of a Nation Arc has quite a few:
** [[spoiler:The 2 seconds still image of how the Bafuku sent Gintoki, Katsura, and Takasugi their beloved teacher's head after they executed him is truly riveting. After that still image, it's truly a miracle that Gintoki and Katsura end up relatively sane after the war in comparison to Takasugi, who's gone on a world-ending rampage.]]
** The flashback of [[spoiler: Gintoki's sensei and adoptive father being taken away from him, and how he tries to calm Gintoki by telling him that he'll be back very soon... while also asking him to promise to protect all their friends while he's gone.]] Made even worse when you realize that most serious arcs, all the times we have seen Gintoki risk his life for someone, especially when we didn't understand why he did it when it was just some random kid he didn't know anything about or the old courtesan in this very arc... it's because of the simple fact that [[spoiler: ''he never comes back.'']]
** [[spoiler:Maizo and Suzuran's tragic love story in general, but the end of the arc deserves special mention. They're finally reunited after so many years of being apart, only for both of them to die ''just as they meet again''. It's not all bad, as Maizou's spirit walks with Suzuran in his arms into the afterlife, but it's still one hell of a tear jerker.]]
* The whole damn arc with Hajime Obi "returning" and Otae's and Shinpachi's unbridled joy at having their older brother figure back. [[spoiler:The whole thing literally ends in a giant flaming ball crafted from the tears of fans. Dammit Sorachi.]]
* Kondo's flashback arc with his teacher. It's a short, touching arc, especially this line : "It's a warm handcuffs..."
* Tama is able to be friends with machines, as it was shown some times before in the series. Long story short, there's a chapter where she befriends a malfunctioning cigars' vending machine from a local shop that was going to be shut down soon. She spends all the chapter talking to it, reassuring it would be fine even if the shop was going to close. [[spoiler:The shop closes, it gets torn down]] and Tama still gave it some refuge... [[spoiler:until the moment it is retired and thrown to a local litter... and it finally gives it up]]. ''She'' is still there, protecting it from the rain, no matter how things ended up [[spoiler:and the rain made it like she was ''crying'' too]]. How does Sorachi make a story about a machine and we end up crying over it?!
* The reveal that [[spoiler: '''[[TheHero Gintoki]]''' was the one to kill Shouyou-sensei.]]
** Perhaps even more heartrending is just how much of the different light this paints EVERYTHING in the manga. All of Gintoki's speeches, Takasugi's hatred, Gintoki's promise with Shouyou, all of it.
* Chapter 524 ends the Shogun Assassination Arc with a heart-destroying ending. [[spoiler:Despite everyone's efforts to protect the Shogun as he and his sister goes to hiding, two weeks later he gets attacked AGAIN with a poison needle by one disguised as his retainer and this time, [[YankTheDogsChain the poison already spread into his body]]. He spent his last moments with his sister who ''doesn't know he is dying'' as she made tea for him. His last words to her was that the tea was lukewarm while ''he smiled'' and he rests his head on her lap, Soyo wished him a good night as he rests peacefully... at last as a big brother. The worse part? He kept his coming death a secret from her and her friends. He dies not as the Shogun, but as Shige Shige. In other words, the freaking Shogun... is ''gone''.]] Fans are practically asking how is this even a gag manga anymore? You maniac gorilla, you blew our hearts up! Damn you! Damn you to Hell!
** In the next chapter it turned out that the assassin sent to [[spoiler:Shige Shige was actually his former ''childhood friend'' who might have been forced to murder him and then when he did the deed, he poisoned himself.]]
* Chapter 525 pretty much confirms that [[spoiler:Shige Shige is really dead. The funeral is going on and we see his supporters marching through the street, along with Soyo who didn't took the news well as she found out eventually while Kagura sees her. Zenzo thinking about how all his efforts to save him was all in vain.]] And to make these [[SarcasmMode MUCH better]], [[spoiler:Nobu Nobu orders Matsudaira and Kondo arrested and sentenced to execution for Shige Shige's death.]]
* Chapter 526. [[spoiler:Hijikata and Okita of all people have HeroicBSOD as Shige Shige is dead, Kondo is arrested and about to be beheaded, and that the Shinsengumi is disbanded under Nobu Nobu's orders. Kondo purposely sent everyone to the funeral just so they can't resist his arrest because Nobu Nobu would have brand them as traitors as planned. With their HQ off-limits, they are without a home because their HQ ''is'' their home.]]
** From the start of the chapter, [[spoiler:Hijikata witnesses the display of Kondo's head as he was decapitated. Thankfully it was a dream but seeing that made a lot of fans bawl because they thought he really was gone and showed they do care.]]