Karthus is an AP based champion who excels in teamfight and global nuke (Kill steal). Karthus does not perform well during laning phase against more than dozen of AP champions (ie: Fizz, Leblanc, Kassadin, etc). So it's critical that you try not to die during this time and farm as many creeps as possible so that you are fat enough to be useful in teamfight. Your primary objective for playing karthus is not to die during laning phase, get as many CS as possible, get kill/assist with your R and become an unstoppable force when the game transitions into team fight phase.
Primary Skill To Upgrade : Q (Lay Waste) (you should fully learn this by lvl 9)
Secondary Skill To Upgrade : W (Defile) (Finish this by level 13)
Tertiary skill : E (Wall Of Pain) (last to upgrade)
Ultimate : R (Requime) (Upgrade this at level 6, level 11 and 16
Summoner Spell : Flash & Teleport (Good for ganking another lane) or Exhaust (good for aggressive laning phase & team fight). Both teleport or Exhaust are viable as long as you are using it under the right situation. If you choose teleport you should only use it to gank , save your partners (with wall of pain and disengage) or save a tower. Do not use teleport just to farm that few extra creeps. If you choose exhaust, you can be a little more aggressive during laning phase and have an easier time killing the enemy AP carry together with your competent jungler. In team fight, you can also use exhaust to CC any bruiser that dives on you.
Pre Level 6 Karthus Strategy : Try to stay distant and last hit the creeps with your lay waste or auto attack. Try to harass the enemy AP champion with your wall of pain (W) and lay waste (Q) only when her/his skill shot is on cool down.
Post Level 6 Karthus Strategy : If you take teleport as your summoner spell, you can ask your bot/top lane partners to ward the enemy bush so that you can teleport there to gank, hopefully with you jungler to secure kill. Always look out for any enemy heroes that are low in health so that you can R them to get kill.
Team fight : With proper items, Karthus is a monster in team fight with insane DPS and nuke damage with his R. Try to aim your Wall Of Pain to slow the enemy team's AP/AD carries and immediately trigger your defile, Q & flash in if necessary to deal massive damage. The enemy team will focus you down quickly but if you have Zhonya Hourglass, you can delay your death by 2.5 sec with your defile still on doing damage to the surrounding enemy heroes. Once you are killed, press Q more to damage the enemy team further before using your ultimate while your passive skill, death defied is still on.
My favorite items during laning phase/early game are : Boot Of Speed, health Potion, Tear Of the goddess & Catalyst The Protector.
My favorite items during mid game are : Sorcerer Shoes, Rod Of Age, Seraph Embrace & Rabadon DeathCap.
My favorite items during late game are : Sorcerer Shoes, Rod Of Age, Seraph Embrace & Rabadon DeathCap, Zhonya Hourglass. Be sure to activate your Zhonya Hourglass in team fight when you are almost dead to maximise your DPS!
My Karthus Masteries :
Runes : 9 X Greater Mark Of Magic Penetration, Greater Seal of Mana regeneration, 9 x Greater Glyph of scaling cool down reduction, 3x Great Quint of magic damage
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