Twine opened the scoring inside 15 minutes, converting at the far post from Watters' delivery, before turning provider for the striker who doubled the hosts’ lead.
It was game over just after the half-hour mark as Twine got his second, MK’s third with a beautiful free-kick from 20-yards.
Despite a better second half performance from The U’s, the hosts did get their fourth 13 minutes from time, with Watters volleying home from inside the box.
Sam Smith did give the visiting supporters something to cheer about with a neat finish, but it was far too little, far too late as The Dons ran out comfortable winners.
Story of the game
The game started with neither team really getting a foothold on the ball, with Watters and Ironside looking to get hold of the ball upfront for their respective sides early on.
The excitement levels rose every time Twine found himself on the ball, with the visitors affording the attacking midfielder too much time.
And he found himself with a bit of time at the back post after a cross from Kioso was headed more up than away, but he didn’t pull the trigger and the chance was gone.
But MK did get their opener minutes later.
Watters chased onto a long ball from O’Hora and his first time cross found the sliding Twine at the back post to tap home to give the hosts a deserved opener.
The former Swindon Town man was finding himself in acres of space, getting another opportunity at the back post but this time his effort was blocked.
Cambridge grew slightly into the game, Wes Hoolahan trying to get himself on the ball, but nothing was happening ahead of the veteran Irishman.
The hosts stayed on the front foot scored their second through the combination of Watters and Twine once again.
This time it was the forward who was played in by Twine and he placed his shot across the diving Dimitar Mitov into the bottom right corner.
The hosts came again with a sustained spell of possession in the final third, with little holes popping up in the Cambridge midfield and defence.
The visitors made a rare venture forward on the counter after Hoolahan did well to keep the ball in his own half, before George Williams’ cross was deflected away to safety.
Once again, though, the hosts found the net despite The U’s little spell of possession.
Dons won a free kick after a little trip on the edge of the box and it was Twine who delightfully curled the set piece over the wall and into the net.
It should have been four before half time as Daniel Harvie found himself with the freedom of Milton Keynes down the left-hand side, his cutback found Twine whose effort was saved and Watters somehow couldn’t turn home the rebound.
The visitors had another effort just before the break when Jensen Weir won the ball back, Hoolahan drove forward and found James Brophy who almost stumbled and fired his effort over the bar.
Cambridge came out after the break and enjoyed a good spell of possession but it was Kioso who had the first chance of the half.
He got in behind Dunk, who came on at half-time, with relative ease and saw his right-footed effort deflected behind for a corner, which eventually came to nothing.
At the other end, Brophy volleyed high and wide from inside the box after a good knock-down from Ironside.
The visiting fans ironically chanted “we’ve got the ball” but their team was much better in the opening ten minutes of the second period.
And the U’s had their tails up as Hoolahan combined with Ironside before slipping in Brophy whose effort was just deflected past the post by Fisher.
From the corner, Dunk forced Fisher into a save low down to his right, but the away side were starting to enjoy the game a bit more.
The hosts settled back into the game and came forward through Kioso again, and his low drive from the right side of the box was well saved by Mitov.
Cambridge hit the bar 15 minutes from time, Sam Smith heading against the upright.
But, once again, it was the hosts who found the net once again.
Jack Iredale’s pass is cut out and it is lobbed through for Watters to run on to and volley past the helpless Mitov.
There was something for the Amber Army to cheer about, Smith finding the net after a good break nine minutes from the end.
The game ended on a sour note with a horrible looking head injury to Cambridge’s Williams, but he was able to walk off the pitch himself with a bandage around his head – receiving a warm reception from his former admirers.
The result takes MK Dons into the playoff places to fifth, meanwhile Cambridge slipped to 12th.