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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.
Karma is one of those rare champions whose role in the game changes as the game goes on. Early game she can dominate a lane with her high burst but as the game progresses her role in team fights becomes much more support oriented. Supplying the team with slows, shields and heals. She can still contribute to a fight damage wise but her strength really shines in supporting others in late-game.
The runes are pretty straight forward.
I run 9/0/21. The mana regen, movement speed and CDR that the support tree offers is the perfect accent to Karma. Really plays to her strengths. If you decide to take Exhaust then obviously switch up the Offensive to reflect that, same with Clarity instead of Flash in the Support tree.
Flash: For more escape options because all she really has is the slow to escape with and more often than not it's on cool down.
Ignite: Great for early game when you need to finish off that fleeing enemy. Combined with her burst and slow, ignite is just the great finishing touch needed. Also great for stopping those hp regen'ing champs late game.
Ghost: Personally, I think it's overkill with Spirit Bond but it's good for when that's on cool down.
Exhaust: In the same boat as ghost, I think it's overkill with Spirit Bond, but shutting down a melee dps is never a bad thing.
Clarity: Early game you don't really have a mana problem but clarity really comes in handy late game when you need to be spamming your spells in a team fight. Combine clarity with max CDR and Karma will be a pretty big force to deal with.
Opening with Doran's Ring has proved to be the best choice for early game. It gives added mana regen, ability power and extra health. Utilizing Mantra+Heavenly Wave to heal combined with all of the mana regen from Masteries and Runes allows Karma to lane indefinitely.
I usually pick up Ionian Boots of Lucidity second if I can afford it (usually can). If not I take boots of speed, health potion and a mana potion.
Now, depending on how well I've been doing early game I make a choice. If I've gotten a few kills then I pick up Soulstealer but if it's been relatively quiet I build Hextech Revolver. I've found that the spell vamp on Hextech along with Mantra+Heavenly Wave provides a very nice heal to myself whenever I attack or heal others.
I buy whichever item I didn't get before and move onto the Will of the Ancients. Always beneficial to help others plus more for Karma plus it's not very expensive after already getting Hextech.
Rylai's Crystal Cepter is a great addition to Karma because the slow stacks and it gives a great deal of survivability that she desperately needs late game.
After that you can pretty much guage what would be the most beneficial to you and the team. I put Rabadon's Deathcap for the immense amount of AP but you can pick depending on the situation.
-Skilling up Heavenly Wave first gives Karma the ability to not only heal herself, deal good AoE damage, heal an ally but it can also take out full creep waves (late game) with one shot. It short cooldown makes it spammable, especially if you have tons of mana regen.
-Karma's passive allows her to surprise champions trying to gank her. Luring them in with relatively low health, Mantra+Soul Shield usually surprises them with a big burst of damage along with protecting yourself. Tethering them with Spirit Bond and then Mantra+Heavenly Wave them gives another burst of damage AND heals yourself. This usually turns the tide on any gank and you'll end up running circles around the enemy ganker who thought they had the upper hand.
-Spirit Bond's tether does not cut off over walls so you can speed up an ally that is on the other side of a wall. Keeping you at an even safer distance or assisting a teammate from certain doom.
-Try to tether a unit that is in the back of whatever group you are fighting in. It allows maximum potential to cause Spirit Bond's tether to come in contact with other units; slowing them or speeding them up.