There's a good place to get this on the "Road to Victory" stage. You'll need your Shotgun upgrades at least through the clip size upgrades, as well as have a full clip. Also you'll need ammo for the SMG. When you approach the bathroom for the "Spawn more Deadpool-lords" achievement, stealth kill the normal enemies and let the shield generator enemy go into the bathroom. Stealth kill another normal enemy and there will be a bigger enemy. Get his attention, and lure him into the bathroom with the shield generator enemy. Exit the bathroom and the larger enemy will tend to get stuck, and the shield generator enemy will be in there with him giving him a shield to slow his damage. When he gets stuck, kill the 2 random enemies that are near you and stand behind a pole facing the stuck enemy. Unload all your shotgun rounds into him and you'll be around 250 combo. Switch to your SMG and unload on him until you get to 300. I was able to do this on Veteran difficulty, after having purchased all upgrades. Just try not to shoot the enemy in the head or he'll die too quickly.
Here's a video showing the above mentioned method. Thank you VVh1pCr3am for the video.
I got over a 300 hit combo just after the part when you have to collect some power cores for Cable and it never popped! It was those blue guys with the shield so I could just keep on bashing them. Does it have to be bang on 300?!
For all the people that are having trouble with this, you need to get a combo of more than 300 hits and then dodge until the combo is finished, if you get hit, the cheevo doesn't unlock even if you make more than 300 hits.
Level: Front Gates of Eeeeevil Final Fight: Sinister Difficulty: Ultra-Violence Start unloading with the shotgun on the first two Sinister clones. By that time you should have a x140+ combo going. Use Momentum (I suggest [LB]+[Y] with any melee weapon) to kill the next 3 approaching clones earning you a total of x250+ combo. With a few more shotgun blasts to the remaining clones you should be over the x300 mark. Teleport away from all enemies, without getting hit, and let the combo end in due time. Not an easy achievement to get but doing it at this location allows you to start at the beginning of the fight if you get hit and your combo chain resets.