Hughes began his career at Oldham Athletic making 44 appearances scoring once before joining Notts County, where he made 130 appearances scoring 18 times. At Notts County Hughes helped earn them the Division Three championship.
He joined Reading on 5 July 2001 on a three-year deal as a replacement for Darren Caskey, but Notts County and Reading failed to agree a transfer fee and this was later set at around £250,000 by a tribunal. Hughes became an important player for Reading and helped earn the side promotion to the First Division of The Football League, finishing second in the Nationwide League Division Two. His earlier seasons at Reading had seen him play in his preferred midfield role and he flourished, going on to make 183 appearances and scoring 19 times.
Hughes joined Norwich from Reading on 21 July 2005 for a fee believed to be around £500,000. He endured a tough start to his Norwich career, as his own form and that of the team was poor for much of the 2005–06 season. In 2006–07 season, new manager Peter Grant used him more as a utility player, covering on either wing or full back position. Hughes played 41 games that season.
Hughes moved to Leeds United on a two-year deal on 9 August 2007 for an undisclosed fee. Hughes joined Leeds the same day that the club was docked 15 points in League 1. In an interview, Hughes explained his reasons for leaving Norwich: "Dennis Wise told me the challenge and the position the club was in. He wants fighters and I felt the challenge of playing for Leeds United and Dennis Wise was too good to turn down ... The manager at Norwich told me he didn't want me to leave, but I didn't want to stay and be a squad player."
He scored his first and what turned out to be only goal for Leeds on 19 April against Millwall, tapping in from close range to finish a flowing move that Hughes had himself started on the edge of Millwall's box. His first season at Leeds saw Hughes play an important squad role by being used in a variety of positions, which saw Leeds get to the playoff final against Doncaster Rovers in League One. Leeds lost the game 1–0 and remained in League One. The following season Hughes again was played in a variety of roles, and was mainly used off the bench. Leeds after a stuttering start managed to get into the play-offs after new manager Simon Grayson rejuvenated Leeds. Leeds lost out in the semi-finals of the play-offs against Millwall after losing 2–1 on aggregate.
At Leeds, Hughes was mainly used as a utility player, playing in various positions. He started the 2009–10 season playing for Leeds at left back due to the absence of Ben Parker through injury. Hughes missed a few games himself with an injury but returned to the Leeds side playing in either full back position, eventually ousting loan signing Tony Capaldi at left back.
Hughes played for Leeds against Manchester United when Leeds won 1–0 at Old Trafford on 3 January 2010 in the FA Cup. However, Hughes picked up an injury against Manchester United and was not fit enough to be involved in the following game against Wycombe Wanderers, but returned to the line-up in the next game, against Exeter City. He played left back for Leeds when they earned a 2–2 draw against Tottenham Hotspur in the FA Cup on 23 January.
Hughes played an instrumental part as Leeds were promoted to the Football League Championship after finishing in second place in League One and thus earning automatic promotion. Of the 33 games Leeds won, Hughes started in 32 of them. On 26 May 2010, Hughes signed a new one-year deal with the club.
After being an unnamed substitute against Derby County, Hughes came on as a second-half substitute in the following game against Lincoln City. He also came on as a half time substitute in the 1–0 win against Watford where he played at left back after regular left back Fede Bessone picked up an injury. On 8 January 2011, Hughes came on as a second-half substitute and helped earn Leeds a 1–1 draw against Arsenal. Leeds were 1–0 up from a Robert Snodgrass second half penalty, before Arsenal equalised in the 90th minute when Cesc Fabregas also scored a penalty. Hughes left the club after waving goodbye to the fans after the FA Cup Replay at Elland Road against Arsenal, where he was an unused substitute.
Hughes' totemic status at Leeds was due more to his willingness to work hard in whichever position he was asked to play, his humility, and his rapport with fans and teammates, than to any exceptional football ability. The esteem he is held in by the club's fans is evident in the popular chant 'Andy Hughes is fucking brilliant', and in the continued use of a photograph of him as the website banner of fan magazine The Square Ball, even after he left the club.
On 21 January 2011, it was announced Hughes would join Scunthorpe United on an 18-month contract.
On 1 August 2011, Hughes was transferred from Scunthorpe to Charlton Athletic. He made his debut on 13 August 2011 after coming on as a substitute against his former club Notts County. He made 15 league appearances in the 2011–12 season, however he played his last game of the season in January in a 4–0 FA Cup loss to Premier League side Fulham after sustaining an Achilles injury while playing golf. The injury consequently needed surgery and kept him out until February the following year. After 13 months out with injury, Hughes played his first game in a 0–0 draw in a development squad match against Millwall in which he was one of three over 21 players permitted. He returned to the first team starting line-up on 30 March 2013 in the 3–2 win against Bolton Wanderers, and made his first appearance for the side since returning to the Championship. On 29 May 2013 Hughes signed a new one-year contract to stay with the club till 2014. On 7 May 2014, it was confirmed that Hughes was leaving Charlton.
On 22 July 2014, it was announced that he had joined Football League Championship club Bolton Wanderers as their Professional Development Coach. Hughes also continued his registration as a player with the Bolton squad, taking his career into a nineteenth season.
On 3 October 2014 it was announced that Hughes and fellow coach Lee Turner would take charge of Bolton in the interim following the departure of manager Dougie Freedman. In his only game in caretaker charge, Bolton lost 2-1 at home against Bournemouth
On 11 December 2015, it was announced that he had joined Football League Championship club Rotherham United as their First Team Development Coach.
On the 9 February 2016, it was announced on Twitter that he had left Football League Championship club Rotherham United as their First Team Development Coach with immediate effect.
On 3 March 2016, he joined Crystal Palace's first team coaching setup and took his first session at the club's training ground. Hughes played for Alan Pardew while the duo were at Reading, between 2001 and 2003. Hughes had a positive impact in his short spell with the team keeping its premiership status for a record 4th consecutive season and reaching the FA cup final only to lose to Manchester United in extra time .
On 26 May 2016, he joined fellow Championship side Huddersfield Town as their new first-team coach, replacing the departed Mike Marsh, who joined up with the England national under-17 football team. The decision to bring Hughes in as first team coach proved yet again to be a success and have another positive impact with in the club, assisting David Wagner in gaining promotion to the premier league and creating history in their first full season together.As of 4 October 2014
Division Three Champions: 1997–98
Division Two Runners Up (Promoted): 2001–02
League One Runners Up (Promoted): 2009–10
League One Playoff final runner up 2007–08
League One Champions (Promoted): 2011–12
Leeds United Player of the Year Awards – 2007–08: The chairman's Special Award
Leeds United Player of the Year Awards – 2008–09: Best Contribution to the Community Award
(correct as of 26 August 2012)