Due to how beginner and speedrunner-friendly the game is, it's astounding on how much effort Capcom puts in this game. Enough that Capcom even was nice enough to allow Sequence Breaking methods for newcomers and veterans.
- Much like Resident Evil 2 (Remake) before it, adding a laser sight eliminates the pause before aiming is focused, and completely eliminates the loss of aiming when in motion. Leon/Ada no longer has to aim down the sights and the bullet just goes wherever the red laser points.
- In the beginning of the game, the belltower of the church is visible from the village, and it's possible to make it ring by shooting it with a sniper rifle or a rocket launcher. Should a player bring their sniper rifle in to New Game Plus and shoot it during the village attack, the fight will end immediately, just as in the cutscene where the Plagas ring it themselves.
- Some boss fights can be cheesed if you know what you're doing. The bolt thrower's mine bolts can be used on a light bulb to kill the Bella sisters immediately after the cutscene ends. The same tactic can be used on El Gigante's first fight and Méndez.
- Speaking of El Gigante, when Luis leaves to grab a stack of dynamite to damage the armored giant during the double El Gigante fight, he will make a comment if you manage to kill both of them before he returns.
- In normal gameplay, the first armored El Gigante has to be beaten using a cannon on Salazar's castle walls. But if you saved a rocket launcher on your person, you can defeat it immediately after it spawns and avoid having to deal with its attacks.
- Due to how in-game cutscenes work, you can actually kill enemies during cutscenes while they're chanting, and any explosives you use will go off as intended. This has its most notable use in the castle gallery room where you need to obtain the Goat Head to advance. Normally, a brief cutscene will play where a zealot pulls a lever to lower the bridge you are standing on while a red zealot walks into view, but if you throw a grenade at them before the scene starts he can't actually activate the mechanism and you can speed past an otherwise difficult fight.
- If you read the file on Salazar, then it's possible to end his fight with two golden eggs. Salazar is deathly allergic to eggs, and golden eggs take 75% off his health, allowing you to end the fight quickly. Even just a single one can make the fight a breeze.
- When playing The Mercenaries as Krauser and activating his Plaga arm at least once, his sleeves will remain torn for the rest of the round.
- Both Leon and Ashley won't react to flashbang grenades if they're wearing any of the unlockable sunglasses accessories.
- In Chapter 3, the Ganado that Leon can spot on a hill while returning to the Village plaza from Mendez' house is the one that releases the first Colmillos after the tower gets bombed down. If the player is quick enough and kills the Ganado before he escapes, he won't release the hounds.
- Some obstacles in the story that requires Leon to destroy something to progress (i.e., the cave-in in the mines, the wall destroyed by the wrecking ball by Ashley, and the anti-aircraft gun attacking Mike's helicopter) can be easily bypassed by using the rocket launcher. The anti-aircraft gun can also be destroyed with enough grenades, even if it is tricky due to the angle, and the destruction of the wrecking ball wall can be sped up by throwing at least three regular grenades at said wall (this can only be done when Ashley enters the wrecking ball and the defense sequence starts as before that the wall is invincible.)
- The Salazar statue that appears when you enter his clock tower and will instantly kill you if you get too close to the flames. Luckily if you have either rocket launcher on your person, it'll go down and rendered useless, making traversing the tower the more easier.
- Normally, Chapter 11 starts with having to make a detour and fight a large mob of Ganados to get dynamite to clear a cave-in. This sequence can be skipped with a rocket launcher, but if Leon clears the cave-in with the rocket launcher and gets the dynamite anyway, the Merchant will buy the dynamite for a few thousand Pesetas.
- Partway through Chapter 5, you can do an optional Side Quest where you have to kill a King Mook of the wolf-like Colmillos in the village square. You'd think you could simply rush up onto a roof and kill the hound from a safe distance, but if you go to an area where it can't reach you it will actually run off behind the barn where you can't see it either.
- During the cabin siege scene in Chapter 5 with Luis, one can collect the boards supposed to be used to barricade the windows and not use it. note If Leon survives the siege and retains the boards, he can sell these boards to the merchant, though for only a few hundred Pesetas per board.
- Though the game's design is speedrun-friendly, there are some measures to prevent Sequence Breaking all the way towards the end. For example, to access Luis' lab in Chapter 15, Leon must obtain Luis' key in the start of Chapter 12, which means unless there is a Sequence Breaking method to bypass this section, players MUST go through the castle mines with Luis to ensure they have the key.
- If you are using invincibility via cheat device or a trainer on PC, instant death triggers will bypass invincibility cheats, such as the gun-turrets in the beginning of chapter 13 and failing a button mashing sequence in the second boss fight with Krauser.
- In Chapter 6 of Separate Ways, Ada comes across the "Defensive Line" which consists of several machine gun pillboxes that Ada has to bypass. The first two are invulnerable in the front, requiring Ada to carefully get around the pillboxes and shoot an explosive barrel through a hole in the back to destroy them. However, if the crossbow has its unique upgrade of increasing the explosion range of its bolts, hitting the front of the pillbox turret can set off the explosive barrels.
- Towards the end of Chapter 7, despite being out of the normal player's path, if you no-clip Ada into the same arena that Leon is fighting the mutated Saddler
, all the hit boxes still work and Saddler's attack can damage Ada. Not only that, but Leon's gun fire will also damage Ada if she gets in the way.
