Not Updated For Current Season
The masteries shown here are not yet updated for the current season, the guide author needs to set up the new masteries. As such, they will be different than the masteries you see in-game.
Role: Lane control and last hitter.
Utilities: Infinite range ultimate, a slowing wall and a lesser version of Crowstorm.
Lane: Always go middle lane, if people complain or deny you then just afk in the pool because you would be just as useful.
[*] (Passive) Death Defied: You should NEVER EVER be in a situation where this ability would be useful. If you do die however, activate Defile, use your mine twice, then requiem if the prey is low on health AND has no way to recover it before the detonation.
[*] Lay Waste: This spell is going to be your best friend until level 12. When laned against a caster (e.g. Ryze) always put this down behind them marginally, if they become wise then improvise (no rhyme intended), and if they are standing far back then just use this to kill off minions. When laned against a melee or someone who has abilities that activate at melee range, deprive them of xp and gold by constantly "mining", and at all times try to stand behind your minions or farther back to avoid Critical Failure.
[*] Wall of Pain: This is Karthus' least useful abilities until rank 5 even then being of little help. If you are teamed with people with stuns this makes their victim's escape denied. Also great for team retreats as it almost always guarantees a successful getaway.
[*] Defile: This is what Kathus says when fiddlesticks says crowstorm. Early on you are getting this ability for its mana efficiency. The bonus mana when you kill a minion is amazing at keeping you in the lane. At rank 5 this spell will become THE way to push lanes because of its tremendous AoE damage.
[*] Requiem: This is your "HAHA KILLED YOU IN ANOTHER LANE" ability. This spell unfortunately has a massive cooldown. I recommend using this when you have obtained a Soulstealer and even then at rank 2 or 3.
[*] Clairvoyance: I pick this up to defend myself from enemy ganks or to check bushes from far away.
[*] Teleport: When you leave your lane use this to get back. At end game use this to switch lanes quickly.
Karthus may be the biggest squishy in the game. You are not the person who even remotely stands up front, in team fights you should try to stand as far back as possible (I recommend completely avoiding team fights altogether).
[*] Early Game (Lv. 1 - 10) You will be babysitting middle lane endlessly so this will get boring until mid game. Go back to base at level 6 to pick up your Tear of the Goddess. Go back at level 8 to get boots or sorc boots. After you have sorc boots then grind your way to soulstealer as fast as possible, that's when Mid game begins for Karthus.
[*] Middle Game (Lv. 11 - Lich Bane) This is the point in most games when people become much more aggressive and ganking becomes more prominent. Whenever you have the opportunity use requiem to gain stacks for soulstealer and push lanes with Rank 5 Defile. Once you have gotten Archangle's Staff and Lich Bane end game begins.
[*] End Game (Lv. 16~) Now is the time for Karthus to truely shine. By now you should have 6+ stacks of soulstealer and be saving up for Zhonya's Ring. At this point you are permitted to move between lanes so long as you KNOW that no one will gank you. Play defensively at all times and hug allied turrets whenever possible. You will draw the enemy team because of your overpowered ability to slide entire lanes in your favor just by taking a stroll, just think accordingly and try to lane with the tank or disabler. Once your team is at the enemy's outer or middle turret stay far back and only attack minions, when there are no minions start attacking but stay aware or you will die. Defending your own turrets is your primary concern, always abandon your target if one of your turrets are under attack and have a chance to be saved. Otherwise, use requiem to stack kills.
If done properly you should always have flawless games and cause much QQ in the enemy team.