The game was only seven minutes old when Port Vale opened the scoring, with Theo Robinson hitting an angled shot past Elliott Parish.
In the second period, Sam Foley doubled the lead as he headed home a Byron Moore cross.
U’s boss Kevin Keen made two changes to his starting line-up, bringing in Alex Gilbey and Jamie Harney for Kane Vincent-Young and Leo Chambers, with the latter picking up an injury in training on Friday.
The start of the game saw both teams sizing each other up but the U’s probably edged possession in the very opening stage of things.
In the first meaningful attack of the game though, the hosts went ahead, with Theo Robinson beating Elliott Parish with an angled shot.
The Vale striker had got on the end of a ball into the left channel, which Jamie Harney will feel he should have intercepted, and his shot looked to bounce up violently to take it over the diving hands of Parish.
For the following ten minutes, the game returned to being played predominantly in the middle third of the pitch, with the U’s more than holding their own.
Both sides had shots from distance either side of the twenty minute mark, Gavin Massey narrowly over for the U’s before Anthony Grant went even closer with his effort arrowing inches wide.
Darren Ambrose and Alex Gilbey then also tried their luck from outside the area, but Chris Neal in the Vale goal watched the first fly comfortably wide before saving the second.
The U’s were asking more of the questions towards the end of the first half, with Ambrose central to proceedings.
He headed just wide from a Nicky Shorey cross and then shot just wide after receiving a pass from Owen Garvan.
That effort was the final one of the first period and the whistle went with the U’s trailing to that early Robinson effort.
Within seconds of the restart, the U’s tested Neal in the home goal, but it was a comfortable save from a George Moncur effort.
On forty nine minutes, the U’s were thankful to their own keeper, as Parish made a fantastic fingertip save from a Sam Foley strike.
His touch pushed the ball onto the crossbar and Parish was on his feet quickly to snuff out the near post cross that followed.
Eight minutes into the half, Keen made a double substitution as he bought Elliot Lee and Nathan Oduwa for Moncur and Massey.
The change didn’t really alter the flow of the play, with Port Vale controlling things and making most of the chances.
Elliot Lee did have a low shot saved in a rare U’s attack but Parish was the busier of the two keepers.
He showed a safe pair of hands with a save from Foley, and then was relieved as he took a weak shot from Hooper when the sub should have squared the ball for an unmarked Grant.
The home side doubled their lead on seventy two minutes, when Sam Foley headed home from a Byron Moore cross, with Parish unlucky as he got fingertips to it before it went in off the bottom of the bar.
Having only lost one game at home in the season, Port Vale were confident of holding onto their lead and that showed in the remaining twenty odd minutes.
They comfortably saw off the U’s, with Grant and O’Connor in central midfield looking extremely diligent in protecting their back four.
The final whistle went with the U’s failing to mount a late charge on the home defence, and going down 2-0 in the Potteries.