Central defender Josh Pollard and forward Eoin McKeown signed their first professional deals ahead of stepping up to the under-23 squad.

[9] Tom Eastman became the first Colchester United out of contract first-team player to sign a new deal on 28 June, agreeing to a two-year extension.

[23] On 14 July, Academy product Macauley Bonne left the club to join National League side Leyton Orient, signing for an undisclosed fee alongside former U's player George Elokobi.

[24] Colchester won their third successive friendly the same day, beating Llandudno 1–0 in north Wales courtesy of a Denny Johnstone goal.

[25] Cole Kpekawa joined Colchester for a second spell on 17 July, signing a one-year deal from Barnsley for an undisclosed fee having featured on loan from Queens Park Rangers during the 2014–15 season.

[30] On 24 July, United were hit by the news that club captain Luke Prosser would be ruled out of action for a further two months after undergoing a further operation on his injured knee.

[35] On 1 August, Colchester made two further under-23 additions, with the signing of Australian goalkeeper Dominic Kurasik from Brentford and former-Crystal Palace left-back Callum Sturgess on one-year contracts.

Mikael Mandron missed a chance to equalise from the penalty spot when his effort was saved by Jed Steer, before an unfortunate Frankie Kent scored an own goal to double Villa's lead on 19 minutes.

[41] On 15 August, Colchester offered new contracts to Brennan Dickenson, Kurtis Guthrie, Frankie Kent, Tom Lapslie and Drey Wright,[42] while winger Dion Sembie-Ferris was released by mutual consent in search of first-team football.

A first-half injury time goal put the hosts ahead and Luton added a further two in the second half to leave Colchester in the relegation zone.

Sammie Szmodics continued his goalscoring form inside five minutes, but Reading equalised through Josh Barrett before taking the lead through Ben House prior to half-time.

Naming an unchanged starting eleven from the side that beat Forest Green 5–1 the previous weekend, the U's fell to a 1–0 defeat on 2 September thanks to a second-half goal from Uche Ikpeazu.

[60] On 16 September, winger George Brown made his debut for East Thurrock United in an FA Cup win against Biggleswade Town after joining the club on loan earlier.

[69] On 16 October, Diaz Wright joined Needham Market on loan until the end of November,[70] while Colchester were drawn at home to Oxford City in the first round of the FA Cup which would be the first-ever meeting between the two clubs.

[77] This was followed up by an EFL Trophy Essex derby defeat to Southend United, who won 2–0 to knock Colchester out of the competition at the group stage for the second successive season.

[78] Returning to league competition on 11 November, Sammie Szmodics scored his sixth goal of the season from the bench to earn Colchester a 1–0 win at Barnet.

[80] Their good run continued on 21 November when Sammie Szmodics again proved the difference with an early goal in Colchester's 1–0 home win against Lincoln City.

[82] Following a two-week break due to their early FA Cup exit, Colchester returned to action in a home match against Exeter City on 9 December.

[83] Forward Nicke Kabamba made an early return to parent club Portsmouth on 14 December after failing to score in ten appearances for the U's.

Incoming were Junior Ogedi-Uzokwe, who had scored 34 goals in 34 games this season and was the top scorer in the Isthmian League, and also left-sided player Ryan Gondoh.

[107] Aaron Barnes arrived on a permanent basis from Charlton Athletic, while Ben Stevenson signed on loan from Wolverhampton Wanderers after joining the Championship side from Coventry City earlier in the day.

[109] On 2 February, Cameron James headed out on loan for the remainder of the season to National League South side and his hometown club Chelmsford City.

Following a goalless first-half with Newport County, substitute and debutant Ben Stevenson scored ten minutes after arriving on the pitch, before Tom Eastman doubled the U's lead after a goal mouth scramble.

[118] Colchester missed an opportunity to take an early lead against Yeovil on 17 March after Sammie Szmodics had an eighth-minute penalty kick saved by Stuart Nelson.

[122] Colchester earned their first back-to-back victories since December with a 2–1 win over promotion-chasing Luton Town at the Community Stadium in their Good Friday fixture.

Late in the second-half, Ryan Jackson fouled Luke Gambin in the penalty area which was converted by Danny Hylton but Colchester held on for victory.

Drey Wright scored within 19-seconds to give the visitors an early advantage, but the U's were pegged back when Tom Eastman fouled Haydn Hollis in the box and Reuben Reid converted.

Drey Wright had opened the scoring within the first ten minutes of play, but a revival in the second half by County through Jonathan Forte, Shola Ameobi and Richard Duffy saw the away side claim victory.

[128] He then stepped off the bench in his next game against Lincoln City to score the equaliser for Colchester after they had fallen behind five minutes earlier to an Elliott Whitehouse penalty.

[129] Goalkeeper Dillon Barnes was handed his first league start for Colchester on 28 April in their final home game of the season against Swindon Town, and he kept a clean sheet as the match finished 0–0.