Having been in their youth schemes since the age of 10, Campbell signed for the Manchester United Academy on 1 July 2004. He made an immediate impact, scoring 14 goals in 22 starts for the Under-18s in the 2004–05 season. His performances for the youth team also led to him playing five times for the reserves, for whom he scored once. He signed his first professional contract with Manchester United on 22 March 2006, and he was named as a substitute for Roy Keane’s testimonial match at Old Trafford on 9 May 2006, in which he was a 75th minute replacement for Kieran Richardson. Later that summer, he scored his first goal for the club after coming on as a substitute for Wayne Rooney in a friendly against Macclesfield Town.

After returning to Manchester United from his loan deal, Campbell scored a volley against Glentoran on 8 August 2007 in a pre-season friendly. He made his senior debut for United on 19 August 2007 in the Manchester derby, after coming on in the 73rd minute for Michael Carrick.

Campbell was sent out on loan again in the 2007–08 season, this time at Hull City in the Championship. He initially joined Hull in October 2007 on loan until January 2008, and scored twice on his home debut in a 3–0 victory over Barnsley. Following his match-winning display against Wolverhampton Wanderers on Boxing Day 2007, in which he scored one goal and assisted another, Hull expressed their interest in extending Campbell’s loan until the end of the season. The loan extension was completed on 28 December 2007.

Campbell finished the season as Hull’s top scorer, with 15 goals in 32 appearances. On 24 May 2008, he played in the Hull City team that achieved promotion to the top flight for the first time in their 104-year history. Campbell provided the assist for Dean Windass’ goal in a 1–0 win over Bristol City in the Championship play-off Final at Wembley Stadium.

In July 2008, Campbell was selected for the pre-season tour of South Africa with the Manchester United first team, and scored the team’s fourth goal in a 4–0 win over Kaizer Chiefs in the final of the 2008 Vodacom Challenge. He also scored the winning goal in Ole Gunnar Solskjær’s testimonial match against Espanyol on 2 August 2008. After the match, United manager Alex Ferguson indicated that Campbell would remain at the club for the duration of the season, stating “Fraizer’s future is here”. Campbell earned his first winner’s medal when he came on as a substitute in United’s penalty shoot-out win over Portsmouth in the 2008 FA Community Shield. On 17 August 2008, Campbell started alongside Wayne Rooney for the opening match of the season in a 1–1 draw against Newcastle United.

On 1 September 2008, transfer deadline day, Hull City bid a club record fee of £7 million for Campbell. However, he instead signed for Tottenham Hotspur on a season-long loan, as part of the transfer of Dimitar Berbatov to Manchester United for £30.75 million. This was contradictory to Ferguson’s earlier claim that Campbell would be staying at United for the season. He explained the deal saying; “Tottenham insisted that he be part of the deal and Fraizer’s signed his own agreement to go there for the year so we’re happy with that.” He made his Tottenham debut on 18 September 2008, coming on as a 56th-minute substitute for Aaron Lennon in a UEFA Cup first-round first-leg match against Wisła Kraków. Within 15 minutes of coming on, Campbell provided Darren Bent with the assist for the winning goal. Campbell scored his first two goals for Tottenham in a 4–2 victory over Liverpool in the League Cup fourth round, as well as setting up his strike partner Roman Pavlyuchenko for the match’s opening goal. On 15 November 2008, Campbell scored his first ever Premier League goal late in a 2–1 defeat to Fulham.

During his loan spell at Hull City, Campbell received his first call-up to the England under-21 team, coming on as a substitute in a match against Poland on 25 March 2008. He scored his first international goal on 18 November 2008 in a 2–0 victory over the Czech Republic Under-21s. He also scored in the second group match of the 2009 UEFA European Under-21 Championship against Spain, in a 2–0 victory on 18 June 2009. He was sent off in the semi-final of the championship against Sweden. Following his under-21 experience, Campbell’s Sunderland manager Steve Bruce urged Fabio Capello to consider Campbell for promotion to the senior squad saying, “the England manager should have a look at him”, also saying “As for England, why not? Why not go with up-and-coming young talent?”

Hull City refused to give up on Campbell and in June 2009 they returned with a £6 million bid for Campbell, which was accepted by Manchester United. However, the striker said he would not decide on his future until completion of England’s participation in the 2009 UEFA European Under-21 Championship.

In June 2009, Manchester United accepted a bid reported as £6 million from Hull City and on 1 July Campbell was reported to have chosen the club over Sunderland. On 11 July 2009, however, he signed a four-year contract with Sunderland after Manchester United had accepted a £3.5 million bid (potentially rising to £6 million) after successfully passing a medical earlier that same day. He scored his first goal for the club in a 2–0 League Cup victory over Birmingham City. On 28 December 2009, Campbell partnered Darren Bent in attack against Blackburn Rovers at Ewood Park in the 2–2 draw. Campbell scored twice in the FA Cup against non-League team Barrow on 2 January 2010. On 9 March 2010, Campbell scored his first Premier League goal for Sunderland, scoring against Bolton after just 41 seconds in a 4–0 win. The striker also scored in league matches against Aston Villa, Burnley and Birmingham.

Campbell began the 2010–11 season in goalscoring form in pre-season, scoring four goals in a friendly against Hull, and goals against Leicester City and Brighton & Hove Albion. Having forced his way into manager Steve Bruce’s plans, he started the opening match of the new Premier League season, playing the full 90 minutes against Birmingham at the Stadium of Light in a 2–2 draw. He also played the full 90 minutes in Sunderland’s next league outing against West Bromwich Albion at the Hawthorns. However, he sustained an anterior cruciate ligament injury in Sunderland’s 1–0 win against Manchester City on 29 August 2010, which sidelined him for an expected six months. Steve Bruce said “It’s a tragedy. But Fraizer will be back. He’s a larger-than-life character. He was just starting to show what he was about. But make no mistake he’ll be back and he’ll be firing again.” regarding the injury.

Campbell made his return to training in March 2011. Despite having seemingly recovered from the injury, Campbell suffered a recurrence of the ligament injury in the same knee in preparation for a match against Manchester City on 3 April 2011. After undergoing surgery on 20 April 2011, it was learned that Campbell would be out of action for 12 months. This injury ruled Campbell out of action for the remainder of the 2010–11 season and much of the 2011–12 season. Though he was proposed to return in March 2012, Steve Bruce revealed that Campbell was in the frame to return to action around Christmas time – three months ahead of schedule.

Campbell scored on his return for Sunderland on 29 January 2012, coming on at half time for Connor Wickham against Middlesbrough in an FA Cup 4th Round tie where he scored the equaliser in a 1–1 draw at the Stadium of Light. Campbell made his Premier League return on 1 February 2012 against Norwich City, opening the scoring and providing an assist in a 3–0 home win.

On 23 February 2012, despite only scoring six league goals in four years, Campbell received his first call-up to the England squad for the friendly versus the Netherlands. Interim England manager Stuart Pearce had stated his ambitions to select untried young players for the friendly which would take place on 29 February. Pearce had given Campbell all 14 of his under-21 caps. Campbell made his debut as a substitute for Danny Welbeck in the 80th minute, as England lost 3–2 due to an injury-time game-winning goal by Arjen Robben.

On 21 January 2013, Campbell signed for Cardiff City on a three-and-a-half-year deal for a fee believed to be in the region of £650,000. He made his debut on 2 February 2013 against Leeds United, where he scored the only goal of the match in the 64th minute after coming on as a substitute just two minutes before. On 16 February, Campbell scored two goals on his home debut against Bristol City in the Severnside derby, which was then followed by another two against Wolverhampton Wanderers the following week. Campbell was named as the Championship’s Player of the Month for February 2013 after scoring all of Cardiff’s five goals during the month. On the last day of the Championship title-winning season, Campbell scored in a 2–2 draw with his former club Hull, taking his final season tally for the Cardiff to seven goals in twelve appearances. In the second match of the 2013–14 season on 25 August 2013, Campbell scored twice in a famous 3–2 victory at Cardiff against Manchester City, with both goals coming from headers off corner kicks.

Cardiff accepted two bids for Campbell, one from Leicester City and one from Crystal Palace. On 24 July 2014, Crystal Palace completed the signing of Campbell on a three-year deal after matching the release clause in his contract, believed to be in the region of £900,000. He was released from his contract on 30 June 2017.

On 19 July 2017, Campbell re-signed for newly relegated Championship club Hull City on a two-year contract. He made his debut on the opening day of the season, 5 August 2017, away at Aston Villa, in a 1–1 draw. He scored his first goal for the club on 23 September 2017, in an away match against Reading that was drawn 1–1. He left Hull at the end of the 2018–19 season when his contract expired.

Campbell signed for newly relegated Championship club Huddersfield Town on 12 August 2019 on a two-year contract. He made his debut on 21 August as an 84th-minute substitute in a 2–1 defeat away to Cardiff City, his former club.