Enemies champions will often try to and mostly WILL avoid your second and third modified attacks. Either force them to burn a Flash or an escape skill with your E, or leave the last modified attack to the enemy laner. It will still deal double the damage of the previous 2 attacks, and even if dealing only half the full damage, it is still a lot of damage.
Building at least 1 attack speed item can guarantee at least 2 hits of your Q. Also, if you manage to get your opponent distracted, you might land all three hits.
It is not easy, but a trick to hide your Q is with your Harvester of Sorrow's unique sound. With good timing, you might be able to "hide" your first Q sound effect during a trade, and may hit your full combo.
Guinsoo's Rageblade has immense power and sinergy with this skill. Not only it increase Mordekaiser's attack speed while attacking with his Q activated, it also increase both his AD and AP, both which Mace of Spades use for scaling. Each attack will increase the damage more and more, and the last hit will surely be devastating.
Use the healing propeties to counter the health cost during the laning phase. Minions don't heal as much as champions, but it is better to not try to heal from the opponent laner. You might end with even less health.
Zone your opponent laner by using Harvesters of Sorrow on a melee minion. The AoE is not big enough to counter ranged champions, but against melee champions, it might force them to think twice on last hitting a minion.
Use this skill to coordinate ganks. Mark your jungler and walk towards the enemy laner and try to put him between you and your jungler. The bonus movement speed will kick in and your jungler will come even faster in the lane.
If you are controlling the Dragon's Ghost, Harvesters of Sorrow will form an enormous AoE.
Siege Minions' AoE when marked by this skill has the same size of a marked champion's AoE. Use this for poking. Also, the minion can be healed as well, which might help it sustaining at least 1 more turret shot.
Most Mordekaiser players prefer to pick this skill first due it's extra shield generation and poking potential. However, don't use it too much, or you might see yourself forced to pop a health potion or level up your Harvesters of Sorrow next to heal, which delays your burst potential and might cost you some CS and even cause your death.
During teamfights, this skill is what keeps Mordekaiser's Iron Man shield up. At its max level, it will generate 25% of your maximum shield for every champion hit, so it means hitting 4 champions will fully charge your shield. The low cooldown, which is even lower with some CDR, will frustrate the enemy team most of time because your shield seems to always be up.
In lane, this ability offers a massive amount of sustain in an all-in situation or when fighting against a gank. If in a situation against multiple enemies, focus down an easy to kill target and gain their ghost.
Coordinate with your team to focus down a high priority target, and make sure to use your ultimate on them either at the start of a fight or when you know for sure they will die before the duration runs out. Start with the ability if the target is squishy and easily killed, but use it a bit later if the target has more survivability.
Always use the ability on the highest threat of the enemy team, for example a strong marksman. When killed, your team will have a massive advantage and you will be able to focus down everyone else very quickly and take important objectives.
Try to prioritise marksmen and champions with steady basic attack based DPS such as Tryndamere, as the ghost will not be able to use abilities.
The ghost makes Mordekaiser skilled at tower diving, a tank ghost can take the tower hits until Mordekaiser gets in range to use his Q, and an ADC ghost can keep attacking the enemy or the tower, and charge Mordekaiser's passive shield so Mordekaiser can survive the tower's attacks.
Liandry's Torment synergises extremely well with all his abilities for the extra burn and the extra maximum health damage on enemies. Especially when combined with Rylai.
Rylai's Crystal Scepter is worth considering most of time, as it provides a slow that remedy Mordekaiser's lack of CC and allows him to better stick to enemy targets.
Trinity Force is a viable option. Not only it is one of the few viable cooldown reduction options avaliable, but Mordekaiser has one of the highest base AD in the game, allowing for very powerful Spellblade procs. The movement speed helps with Mordekaiser's lack of mobility and the attack speed is useful to proc Mace of Spades faster.
If you plan to build Mordekaiser tanky, consider purchasing Dead Man's Plate, as it helps with Mordekaiser's mobility issues, making him less vulnerable to kiting.
Hextech Gunblade is a viable item because not only it gives both AD and AP, but also gives omnivamp, which works well with Mordekaiser's kit (alleviates his mana costs, he already has sustain on his kit, etc) - The active slow can also help stick to enemies better.
Despite this, Hextech Protobelt-01 is a viable alternative, as it is cheaper, is one of the few cooldown reduction options avaliable, and the active can help close the gap against an enemy.
Zhonya's Hourglass's active is invaluable in certain situations, as Mordekaiser can easily be focused due to his lack of mobility.
Certain AD items are viable on Mordekaiser due to him having high AD ratios on two of his abilities. Maw of Malmortius provides good defense against magic damage, Sterak's Gage gives Mordekaiser a shield which helps against burst damage and his base AD is high enough that Morde will get a lot of AD from its other passive. Guardian Angel can give Mordekaiser a second chance during fights, and Mercurial Scimitar helps against CCs, especially suppression (as it can't be reduced by tenacity).
Spirit Visage provides defense against magic damage and increases Mordekaiser's sustain. It is best used when paired with other sources of health sustain, such as the rune Ravenous Hunter and/or the item Hextech Gunblade.
Sunfire Cape can help clearing waves, and provides even more damage if you manage to stick close to an enemy. It synergizes well with Harvester of Sorrow. However, it is usually overlooked in favor of Dead Man's Plate, as it doesn't help with Mordekaiser's mobility issues.
Thornmail and Morellonomicon are the two most viable options to inflict Grievous Wounds on an enemy. While Morellonomicon provides Mordekaiser more damage potential, and is more useful against casters (especially AP casters), Thornmail provides more tankyness, and Mordekaiser can build the component Bramble Vest early.
Mordekaiser has no mobility abilities. This means that in laning phase Mordekaiser can't escape ganks at all, and due to the nature of his abilities pushing the lane heavily, he is usually very weak to ganks.
Any crowd control leaves Mordekaiser unable to build up his shield and makes him an easy target to burst down. Prioritise using any crowd control abilities on a Mordekaiser and burst him down before he is able to put out his massive damage combo.