I imagine it's possible to stack this with the achievement for killing a boss in 1 turn.
But that is a harder achievement, if you want to go after this achievement on its own. I recommend a barricade deck with the Ironclad. But there are probably many ways to go about this
Should also note, I believe bosses only count as the big encounter at the top of each area, Elites don't countMethod 1 - Ironclad Barricade
You need barricade in your deck so that block does not disappear each round. Upgrading the card can also help in activating it as it reduces cost from 3 to 2
Then you need a way to build up block quickly. Impervious and Flame wall can help, but any source of block will do. Entrench helps a lot also, expecially when the numbers start to get big, doubling block can be huge.
Then you just need to hope you can set up your block before the boss can do any damage to you
If you get lucky, you might encounter the council of ghosts event. You go down to half max health, but you get 5 Apparition cards that can make you intangible. what this means is, whilst you are setting up barricade, you can make yourself intanglible, so the enemy can only do one hit per attack. easier to block all incoming damage and means less of your block is spent each turn. With luck, by the time you run out of Apparition cards, you should have enough block to tank anything the boss throws at you.
Then you just need something to kill the boss with. Body Slam works great with a high block build. But anything works so long as you can tank anything from the boss.Method 2 - Blod Boss
If you can build up your damage output fast enough in the first area, and you get the Blob Boss. You can exploit it's division effect.
Good cards to have include Flex, Inflame, Limit Break
As well as anything that does good damage for low cost, and anything that can apply vulnerable
When the blob goes to half health, it gets interrupted and splits in two. So any attack it was doing is cancelled and it losses a turn. Whatever health you leave the big blob on, its divided forms have this health
it's first two turns are usually not damaging, so if you can do half health damage in three turns, it won't get to attack you this phase. You want to aim to do as much damage over half as you can. Ideally, get it to just about half health (about 70) within two turns, then do as much damage as you can to get it as close to zero as you can. if will be split into two, the lower the starting health of these, the better. These two blobs can also be interupted by doing half health damage, do bear that in mind. You can if you like, let them do status effects whilst you get them damaged to just above half, then do damage to interupt any attacks you can't block. Just don't let them slime you too much or you might struggle to draw the cards you need to finish them off safely.