Two first half goals from Ben Williamson and a late James Spencer goal secured all three points for Shaun Derry’s men.
Manager Darren Way made one change from the side that defeated Notts County a week earlier with Francois Zoko dropping out with a calf injury. The striker was replaced by loanee Brandon Goodship.
The home side started well and opened the scoring after just four minutes when a cross from the left wing from Harrison Dunk was converted at close range by Ben Williamson.
The goal from Cambridge was the first goal Town had conceded in just under eight of football.
With ten minutes on the clock Town were reduced to ten men when loanee Liam Walsh saw red when referee Swabey saw an off the ball incident and dismissed the young midfielder.
On the half hour mark Yeovil had keeper Krysiak to thank when he pulled off a full stretch diving save to deny a curling free-kick from Zeli ismail.
Right on half time Williamson doubled his and the home side’s lead when he tapped in at the back post in what was nearly a carbon copy of the first goal.
At the half time interval Town made their first sub of the day with Kevin Dawson being replaced by former Cambridge man Ryan Bird.
Substitute Bird found himself through on goal just after the hour mark, but with him just about to shoot at goal the home side defence regrouped and cleared away any danger.
On 70 minutes Town made their second sub with Jack Compton making his return following a long lay off with an injury to replace Harry Cornick.
The home side and Williamson had the ball in the net again on 75 minutes, but the referee’s assistant had his flagged raised for offside.
With three minutes remaining the home side made it 3-0. Another cross from Dunk was met by Spencer, but his initial header was brilliantly saved by Krysiak only for Spencer to slot the rebound home from close range.
Just moments later at the other end Town nearly pulled a goal back when Compton’s long range effort was tipped wide by Norris.