During the 2010–11 season, Fryers suffered a serious knee injury that kept him out for most of the season. Fryers made his senior debut for Manchester United in the League Cup on 20 September 2011, starting alongside Michael Carrick in central defence in United's third round 3–0 victory over rivals Leeds United. He then played in their 3–0 fourth round win against Aldershot Town on 25 October, appearing as a left back. On 2 November, he was a late substitute for Jonny Evans during a 2–0 win against Oțelul Galați in a Champions League group stage match at Old Trafford. He made his Premier League debut in a game against Wolverhampton Wanderers, coming on as a substitute for Patrice Evra in the 68th minute; the game finished 4–1. On 26 December 2011, Fryers continued to press for more inclusions as a 46th-minute substitute for Jonny Evans in a league match against Wigan Athletic. In February 2012, Sky Sports carried a story suggesting that Fryers could follow fellow academy product Ravel Morrison out of Old Trafford at the end of the 2011–12 season. On 4 July 2012, Sir Alex Ferguson stated in an interview: "We haven't heard anything from Zeki Fryers, I don't know what's happening there but he's not been in touch with the club. His agent hasn't been in touch with the club and I can only assume he'll be back for training."
Fryers spent the summer training with Tottenham Hotspur ahead of a proposed transfer, but the two clubs were unable to agree on a compensation package. Belgian club Standard Liège also expressed interest in Fryers, and as they are not an English club, they did not have to pay Manchester United the same level of compensation. Fryers signed a two-year contract with Liège on 23 August 2012. Fryers played in seven matches for Standard, but with the sacking of Ron Jans in November, he was left out of the squad and ultimately reported to his agent that he was homesick.
Tottenham Hotspur
With Fryers out of favour in Belgium, Tottenham renewed their interest in him in the January 2013transfer window and reached an agreement with Standard Liège to sign him. The transfer was criticised by the then Manchester United manager Sir Alex Ferguson, who accused Tottenham of "blatant manipulation" of the rules, having attempted to sign Fryers directly from United in the previous transfer window. Upon signing, Fryers was made part of Tottenham's development squad. During the Asia Cup competition, in July 2013, Tottenham brought Fryers on as a substitute, where he played at left back for the remainder of the game.
On 1 September 2014, Fryers signed a three-year deal with Crystal Palace for an undisclosed fee. The defender was released from his contract on 30 June 2017.
Loan moves
After making only one 3 minute substitute appearance in the League for Crystal Palace, Fryers joined Rotherham United on a one-month loan on 16 January 2015. On 26 March 2015, Fryers signed for Ipswich Town on loan until the end of the 2014–15 season, alongside Crystal Palace teammate Jonny Williams.
On 1 July 2017, it was announced that Fryers had joined Championship club Barnsley on a three-year contract. He was released by Barnsley at the end of the 2018–19 season.
Swindon Town
After his release from Barnsley, Fryers signed for Swindon Town on a two-year deal. Fryers scored his first goal for Swindon Town against Carlisle United in 3–2 victory.
