First half goals from Folivi and Clampin earn the U's a valuable three points as Mullins' side hold on against the Saddlers.
The U's had to come from behind to grab all three points against Walsall, after James Clarke had put the visitors ahead in the opening ten minutes.
But a scrambled goal from Michael Folivi and a superb volley from Ryan Clampin mean that Colchester United take all three points at create a larger gap to the bottom two.
Colchester United boss Hayden Mullins opted for three changes to the team that started at Boundary Park just over a week ago.
Coming into the team were Shamal George, Noah Chilvers and Michael Folivi, with Dean Gerken, Tom Lapsile and Courtney Senior all dropping to the bench.
The U's started the game on the front foot, looking to get ahead of the visitors early on.
And they nearly broke the deadlock within ten minutes. Callum Harriott's effort went agonisingly close to opening the scoring, as he bent a shot towards the top corner, only to see it bounce out and away.
But it was the hosts who opened the scoring. After Osadebe's effort was brilliantly blocked away for a corner by Welch-Hayes, the set piece was lofted to the back post for an easy finish for James Clarke.
The goal seemed to spur an already fierce looking Colchester United side into further attacks and pressure up front.
Michael Folivi was proving a handful for the centre halves of Clarke and Sadler, going close with an acrobatic effort moments before striking the equaliser.
From a corner, Frank Nouble's effort struck the post after Tom Eastman was able to recycle the ball. And Folivi was in the right place at the right time to capitalise on the effort and tap beyond Rose into the unguarded net.
Folivi could have added a second before half time when he saw his effort drag wide, but it was Ryan Clampin with his first ever league goal for the U's that put them in front.
A sumptuous volley from the edge of the area nestled in the bottom corner bringing a roar from the bench as the U's headed to the changing rooms at the break leading 2-1.
Callum Harriott had to be withdrawn at the break due to an injury he picked up at the end of the first half, with Ben Stevenson coming on to replace him.
The U's continued where they left off for the most part, creating plenty of chances.
Michael Folivi thought he had added a second for himself and a third for the U's from a corner just before the hour mark. Frank Nouble's flicked header was met at the back post with the U's thinking the ball had crossed the line, although the referee waved play on.
There was significant pressure on George's goal as the U's looked to hold on to the lead, although there were chances for Hayden Mullins' side on the break.
Both Folivi and Wiredu saw efforts blocked inside the area with less than twenty minutes to go, before further changes were made.
Wiredu and Folivi were replaced by Brown and Senior, with the U's bench looking to freshen things up with some new legs.
It was a tense and nervy final few moments in the game, with the five minutes added time seemingly going on forever, Colchester United were able to hold on and claim all three points.
Colchester United remain in twenty-second place, but now sit on forty-four points with just four games to play, including the Essex Derby against Southend United on Tuesday evening.
Colchester United Starting XI: George, Welch-Hayes, Smith, Pell, Harriott (Stevenson 46'), Chilvers (Lapslie 90'), Eastman, Clampin, Wiredu (Senior 77'), Folivi (Brown 77'), Nouble.
Unused Subs: Gerken, Doherty, Sowunmi.
Walsall Starting XI: Rose, Melbourne, Sadler, Clarke, Kinsella (Bates 60'), Lavery, Gordon, Perry, Osadebe (Osei-Yaw 88'), White, Wright (McDonald 60').
Unused Subs: Roberts, Norman, Leak, Willis.