This can be obtained as early as the second encounter with Destro,near the beginning of the mission.
I did this on Real American Hero difficulty, with Lady Jaye. The first time you knock down Destro is part of the story and can't be missed. After getting to the part where you have to activate three consoles, Destro will show up again and chase you around. The goal is to get rid of all the ads and train Destro around the battlefield, while ignoring the main objective. Do NOT activate any of the consoles as this will spawn in more enemies.
As Lady Jaye, with her special move (B button, by default) you can sprint faster than anyone else, so use this to your advantage any time Destro gets too close. Create some separation, and get some pot shots in with the sniper rifle weapon (the one with 5 shots in the mag) whenever you can. The AI as Sci Fi actually will help out here too, as his main weapon is absolutely monstrous.
You will know when you've knocked down Destro when he makes a groaning sound, falls to his knees, and wraps himself up in an orange protective bubble. After a minute or so he'll get back up and start to chase you around again. Just rinse and repeat until the achievement pops.
Side note: something very fortuitous happened to me during this run. After I knocked him down the second time, he bugged and just stood in place, frozen, for the rest of the encounter. Not sure if this will happen to you but if it does, it makes it even easier.