Tainted Grail: Conquest

When fiest heading out into the Wyrd after slaying a Guardian or beginning a run, the closest combat encounters to the entrance will be marked as "Stray Beast" or something similar. These are battles against a single, weak monster which is what I would recommend for this achievement. I personally did this against an Infected Human, who have 80HP, using the Wyrdhunter class. After you have leveled up and dealt with other encounters, you should have Passive Skills and Runestones that grant extra damage early in a battle, give you more energy or let you draw more cards etc. If you leave one of these encounters just before fighting the first guardian, you should be able to easily deal enough damage in a turn, if you focus solely on damage output and ignore any defensive cards.