Born in Dakar, Senegal, Diouf began his career with Diaraf. In January 2007, he joined Norwegian club Molde, having trained with them in March 2006. He expressed his happiness at joining fellow countrymen Pape Pate Diouf (still playing for a contract with Molde at that time) and Madiou Konate at the club. Molde also agreed with Diaraf all considitions concerning the transfer, if Diouf signed a professional contract with Molde.

In the 2009 season, he scored 16 goals in 29 matches. Even with his strong performance, Molde only finished second in the league and the cup. A highlight of the season was the 5–2 win against Brann on 12 July 2009, where Diouf scored a hat-trick in the first nine minutes of the game, and added the fourth goal in the 27th minute.

In May 2009, he received interest from several senior clubs and on 17 July 2009, Molde and Manchester United announced that a transfer had been agreed for the player. Diouf was loaned back to Molde for the remainder of the Norwegian 2009 season, before joining his new teammates in Manchester in January 2010. “We signed a young player yesterday from Norway, who we’ve been looking at for two years,” United manager Alex Ferguson said. “We weren’t intending on signing anyone else after last week – we feel we have a full squad – but the situation accelerated to a point where other clubs started to make bids, so we had to decide whether we acted or didn’t act. We decided to act and he’ll be the last person we sign.”

On 23 December 2009, Diouf was granted a work permit making him available to play for Manchester United once the transfer window opened in January. After becoming eligible to play for Manchester United on 7 January 2010, Diouf was registered with the number 32 shirt worn previously by Carlos Tevez, and made his debut in a league match away to Birmingham City two days later; with the scores level at 1–1, Diouf came off the bench for Paul Scholes in the 81st minute, but he was unable to help break the deadlock and the match finished as a draw.

On 12 August 2009, Diouf won his first cap for Senegal in a 2–1 friendly win over Congo DR in Blois, France. He scored his first goal for Senegal in a 1–0 victory over Cape Verde on 11 August 2010.

Diouf made his home debut for United in a 3–0 win over Burnley on 16 January 2010, coming on as a 74th-minute substitute for Wayne Rooney. In stoppage time at the end of the game, Diouf scored his first goal for United; after being played in by Antonio Valencia, he looped a header over Burnley goalkeeper Brian Jensen and celebrated with a flip in front of the Stretford End before pointing to the name on the back of his shirt.

On 6 August 2010, Diouf signed for Blackburn Rovers on a season-long loan and was handed the number 41 shirt. Diouf made an immediate impact for Blackburn, scoring within 15 minutes after coming on as a substitute for Nick Blackman in a 1–1 pre-season friendly draw against Hearts in Scotland.

On 24 August 2010, Diouf scored his first goals for Blackburn on his full debut as he netted a hat-trick in a 3–1 home League Cup victory over Norwich City, playing the full 90 minutes at Ewood Park. He then scored his first league goal for Rovers four days later, netting their only goal in a 2–1 home loss to Arsenal on his first ever Premier League start; the assist came from his fellow Senegalese namesake El Hadji Diouf. By the end of his loan at Blackburn, he had made 29 appearances and scored six goals in all competitions.

Diouf returned to United in the summer of 2011, and he was included in the squad for their pre season tour of America. He came on for Michael Carrick in the second half of their first game, a 4–1 win over New England Revolution. In the second game against Seattle Sounders, he came on at half time for Michael Owen and scored in the 49th minute, making it 2–0. The match finished 7–0 to Manchester United. On 5 August 2011, he scored twice in Paul Scholes’s testimonial match against New York Cosmos at Old Trafford. Diouf played in two League Cup matches away at Leeds United and away at Aldershot Town. In both matches, he played on the wing.

Diouf married his girlfriend of four years, Maria Orten, in Molde on 2 July 2011. Diouf went missing for a few days before the wedding, with his fiancée blaming his disappearance on the best man, Molde FK midfielder Pape Paté Diouf. He eventually turned up on 30 June, but Orten was forbidden from revealing the reason for his absence. His brother Mame Mbar Diouf is also a footballer who has played for Molde, Sarpsborg 08 and TSG Neustrelitz. Diouf’s mother, Gnilane, died during the 2015 Mina stampede in Saudi Arabia, while his sister survived with small injuries.

During the January 2012 transfer window, Diouf claimed that Wigan Athletic wanted to sign him on loan so he could get more playing time. Also interested in signing Diouf was Hannover 96. Eventually, on 28 January 2012, Diouf signed for German club Hannover 96 on a two-year contract for an undisclosed fee. Diouf scored his first goal in the 32nd minute in the match against Stuttgart which Hannover won 4–2. He scored the only goal against Club Brugge on 23 February 2012 when Hannover advanced to the round of 16 of the 2011–12 UEFA Europa League. Diouf scored six goals in six games, with a second-half brace in a 4–1 victory over 1. FC Köln on 18 March 2012. In total Diouf played 15 times for Hannover in 2011–12 scoring ten goals including both goals against Atlético Madrid in the quarter final of the Europa League, although Hannover lost 4–2 on aggregate.

On 11 June 2014, Diouf signed a four-year contract with Stoke City beginning on 1 July 2014 on a free transfer. Upon signing for Stoke, Diouf stated that he feels better prepared for the Premier League following his spell in Germany. He made his Stoke City debut on 16 August 2014 in a 1–0 defeat against Aston Villa. Diouf scored his first goal for Stoke on 30 August 2014 against Manchester City, where he ran 70 yards before slotting past Joe Hart to earn Stoke a 1–0 victory at the Etihad Stadium. On 28 December 2014, Diouf scored both goals in a 2–0 win over Midlands rivals West Bromwich Albion. In his first season at Stoke, Diouf has been played out of position at right wing by manager Mark Hughes. He scored in wins against Aston Villa, Everton and Southampton. Diouf played 38 times for Stoke in 2014–15 as the Potters finished in 9th position for a second season running and they ended the campaign with a 6–1 victory against Liverpool with Diouf scoring twice to end the season as top scorer with 12.

On 15 November 2014, Diouf scored in a 1–0 win against Egypt which saw Senegal qualify of the 2015 Africa Cup of Nations. At the tournament finals, Diouf scored Senegal’s equalising goal as they defeated Ghana 2–1 in the team’s opening match.

Diouf began the 2015–16 season well scoring in draws against Tottenham Hotspur and Norwich City in August and the winning goal against Bournemouth, in September to secure Stoke’s first win of the campaign. However following the death of his mother in September 2015, Diouf lost his form and consequently lost his place as centre forward with Mark Hughes instead using him in a winger role. Diouf even had to fill in a right-back against Bournemouth in February 2016, following injuries to Phil Bardsley and Glen Johnson. He scored a late equalizer against Chelsea on 5 March 2016, earning Stoke their first Premier League point at Stamford Bridge. Diouf ended the season by scoring the winning goal against West Ham United, which secured Stoke 9th position. Diouf dedicated his goal to his mother. In 2016–17 Diouf played in 28 matches, scoring once against Bournemouth on 6 May 2017 as Stoke finished in 13th position. Throughout the campaign Diouf again played out of position including as a right-wing back.

Diouf signed a new three-year contract with Stoke on 14 September 2017. Diouf was a regular in 2017–18, making 37 appearances, scoring six goals as Stoke suffered relegation to the EFL Championship. He came in for heavy criticism from supporters during the campaign for his poor finishing. Diouf made 16 appearances in 2018–19 of which only seven were starts and speaking in February 2019 Diouf admitted he would probably have to leave. He was initially not allocated a squad number for the 2019–20 season by Nathan Jones but was restored by new manager Michael O’Neill in November and subsequently scored the winning goal in a 2–1 victory against Wigan Athletic. Diouf remained on the fringes of the squad in 2019–20 and when the season was extended into the summer due to the COVID-19 pandemic, Diouf signed a contract extension to cover the remaining matches. With Stoke securing their Championship safety in the penultimate game of the season, Diouf asked to be released early from his contract on 20 July 2020 after spending six years with the club.

In May 2018, he was named in Senegal’s 23-man squad for the 2018 FIFA World Cup in Russia.

On 31 August 2020, Diouf signed a one-year deal with the newly promoted Turkish Süper Lig side Hatayspor.