Born in Basyoun, El Gharbia, Egypt, Elmohamady started his youth career at Ghazl El-Mahalla in 2003. He started to play for the first team in 2004 at the age of 17. Two years later, he joined ENPPI.

Although he started his career as a striker with Ghazl El Mahalla, he played as a right-sided defender after joining ENPPI. He was selected by the Egyptian national team’s manager, Hassan Shehata, for his first international appearance in 2007.

For a long time, Elmohamady attracted the attention of several European clubs. However, ENPPI was reluctant to allow him to move to any of them. In summer 2007, ENPPI turned down an offer from Hertha BSC, because the German side failed to meet the Egyptian club’s financial demands. The player refused another bid from Rapid București of Romania in 2007.

Elmohamady played several times for U21 Egypt national football team, and was a participant in the 2007 African Youth Championship which was held in Republic of the Congo – he was the rising star of the Egyptian team and one of the stars of the tournament despite his playing out of position as he played forward.

He made his senior international debut in August 2007 at the age of 20, in a friendly against Ivory Coast in Paris and has played eight of Egypt’s last nine matches before ACN 2008. He’s included in the final squad of Egypt which competed in ACN 2008 in Ghana and grabbed the cup, where he played a role as a substitute. Since then, he reserved his place in the starting line up as a Right-back or Winger. He started all Egypt’s six matches in the second round of FIFA World Cup 2010 Qualifiers.

On 25 November 2008, Elmohamady completed a five-day trial with Premier League side Blackburn Rovers following Rovers’ manager Paul Ince’s request. Rovers’ new manager, Sam Allardyce, sent a senior official to Egypt to initiate talks with the Egyptian club in January 2009. However, the deal fell through as Allardyce believed it would be difficult for Elmohamady to make immediate impact.

Elmohamady impressed Sunderland manager Steve Bruce while on trial with the Premier League side in August 2009. However, on 31 January 2010, Sunderland failed to sign him. Belgian side Club Brugge were also interested in the player and had, according to ENPPI, already made an offer. ENPPI accepted loan bids from both West Bromwich Albion and Sunderland for Elmohamady but while West Brom’s offer was larger, Elmohamady chose to go to Sunderland, after being on trial.

In the 2009 Confederations Cup, he was sent off in Egypt’s opening match against Brazil for deliberately handling Lúcio’s goal-bound effort in the last minute, in an effort to save his team losing in the last minute. This resulted in Brazil going on to score the penalty to win the match by 4–3.

On 1 July 2010, Elmohamady joined Sunderland after passing medicals for a season-long loan move from ENPPI for a £500,000 fee, with an option of a permanent deal for £2 million next summer.

Elmohamady made his debut for Sunderland in their 2–2 draw with Birmingham City on 14 August 2010. He won Man of the Match for his performances against Arsenal and Manchester City. Due to his impressive start at Sunderland, manager Steve Bruce expressed an interest in signing Elmohamady permanently in the January transfer window.

On 11 March 2011, Sunderland announced that they have taken up the option of a £2 million transfer which was included in the loan agreement, making Elmohamady’s contract a permanent one on Wearside. On 9 June 2011, the permanent contract was officially confirmed by Sunderland, with Elmohamady signing a deal which will keep him at the Stadium of Light until 2014. Manager Steve Bruce added, “Ahmed has done well in his first season with the club and has shown plenty of potential. We look forward to helping him grow as a player and I think there is much more to come from him.”

Elmohamady started Sunderland’s first league match of the 2011–12 season away to Liverpool, and provided the assist for Sebastian Larsson’s debut goal as the Black Cats drew 1–1. He scored his first goal from a header for Sunderland in a 2–2 draw against West Bromwich Albion on 1 October 2011. Elmohamady fell out of favour following the departure of Bruce in December 2011 and made no starts under his replacement, Martin O’Neill. At the end of the 2011–12 season, Elmohamady had made 18 appearances in the entire season.

On 30 August 2012, Elmohamady moved to Hull City of the Championship on a season-long loan deal, favouring a move which would see him reunited with former Sunderland boss Steve Bruce. On 1 September, he made his debut for the club at the KC Stadium against Bolton Wanderers. On 18 September 2012 he scored his first goal for the club, scoring the first of his side’s goals in a 3–2 victory against Leeds United at Elland Road. He also provided two assists during the derby at Elland Road. On 16 January 2013, Sunderland decided to use the recall-clause. On 31 January 2013 he returned to Hull on loan for the remainder of the 2012–13 season. At the annual awards ceremony on 20 April 2013, at the KC Stadium, Elmohamady was voted as the Player of the Year.

After being on loan from Sunderland for the 2012–13 season on 28 June 2013, Elmohamady signed a three-year contract to become a permanent member of the Hull City squad. He made his debut on the first day of the 2013–14 season in a 2–0 loss away at Chelsea. On 21 September 2013, Elmohamady scored his first goal in the 2013–14 Premier League season against Newcastle United. On 17 May 2014, he played in the FA Cup Final, which Hull lost 3–2 against Arsenal.

On 10 January 2015, in a match away to West Bromwich Albion, Elmohamady touched the ball just before his goalkeeper Alan McGregor picked it up. His touch counted as a backpass, resulting in a free kick for the home team inside the penalty area, from which Saido Berahino scored the only goal of the match.

On 23 June 2016, Elmohamady signed a 3-year extension to his contract at Hull City.

On 19 July 2017, Elmohamady signed for Aston Villa for an undisclosed fee which would see him reunited with former Hull City boss Steve Bruce again.