John Ward was relieved of his duties with the club in the relegation zone but his replacement, former U's defender Joe Dunne, turned around United's fortunes, leading them to mid-table by November.

For the 2012–13 season, the U's marked their 75th anniversary with a special home kit which was designed with the usual blue and white stripes, but did not have a main sponsorship logo.

Freddie Sears scored a brace, but drew 2–2 after an unfortunate Magnus Okuonghae own goal and Theo Robinson's equaliser came as the final kick of the game.

[14] Colchester's league campaign kicked off on 18 August with a 0–0 draw at Preston North End, with Mark Cousins producing a string of saves in the U's goal to preserve an opening day point.

[17] Colchester slumped to their first league defeat of the season on 1 September after they were beaten 4–0 at Tranmere Rovers following a Jake Cassidy hat-trick.

[19] On 15 September, Colchester found themselves bottom of the League One table after six games and no wins following a 2–1 home defeat by Doncaster Rovers.

[20] Their stay at the bottom of the league was brief however, when Anthony Wordsworth's late penalty kick earned them a point during their 1–1 home draw with Crawley Town.

[22] This result proved the final straw for chairman Robbie Cowling as John Ward was sacked as Colchester manager, leaving the club after two years in charge with the U's without a win in League One and 22nd in the table.

[31] On 27 October, Colchester allowed a 2–0 lead to slip to draw 2–2 away at Shrewsbury Town with both goals coming from Arsenal loanees Eastmond and Watt.

Donovan Simmonds scored twice, before Michael Rose's free kick reduced the deficit, but Jamie Slabber's effort late on sealed the win for the Conference South side.

[38] Owing to an early FA Cup exit, Colchester had a two-week break heading into their 8 December home league match against Oldham Athletic.

[41] A further defeat followed at home to high-flying Brentford on Boxing Day, but despite the reverse, a youthful U's side put in a promising display and featured a first professional goal from Drey Wright on his first league start for the club.

[43] On 5 January, Colchester equalled their longest-ever losing run with a 1–0 defeat at Doncaster in a game in which Josh Thompson had a goal ruled out for an infringement by another player.

[44] On 12 January, Colchester set the unwanted club record of nine consecutive defeats as fellow strugglers Scunthorpe United won 2–1at the Community Stadium.

Colchester ended their losing streak with a solid 2–0 victory, with goals from Jabo Ibehre, making his second debut for the club, and Freddie Sears.

[48] Before January was out, the club sold youth-team product Anthony Wordsworth to neighbours Ipswich Town for a £100,000 transfer fee, potentially rising to £200,000.

[49] The U's began February with a 3–2 win against Portsmouth with a brace from Gavin Massey and a Freddie Sears penalty earning Colchester a first away victory since October.

Magnus Okuonghae scored the consolation for Colchester as the U's found themselves three points adrift from safety albeit with a game in hand over 20th-placed Scunthorpe.

[60] On Good Friday, Colchester lost 1–0 to Bournemouth at the Community Stadium, once again leaving the club within three points of the relegation positions with six games to play.

Former U's player Kevin Lisbie scored Orient's goal and had a penalty saved by Sam Walker with twelve minutes remaining.

[63] Jabo Ibehre scored Colchester's goal in a 3–1 defeat at Notts County on 13 April,[64] and then a second successive defeat at home by Milton Keynes Dons threatened to reduced the points advantage over Scunthorpe in their relegation scrap, but with Scunthorpe losing to already-relegated Bury, the U's maintained a five-point advantage and thus requiring a win from their next two games to guarantee safety.