Vaughan signed his first professional contract in the summer of 2005, agreeing to a two-year contract. Early in the 2005–06 campaign, he sustained a knee ligament injury whilst on international duty with England Under-18s. A series of complications sidelined him for the remainder of the campaign and he did not have the chance to establish himself as a regular in the senior squad. He scored his second league goal in the 93rd minute of a 2–0 win over West Ham United. Vaughan suffered a severed foot artery in a match with Bolton.
Vaughan was called up to the England under-19 squad, scoring the winning goal after coming on as a second-half substitute against Switzerland. At the end of the 2006–07 season, Vaughan was named in Stuart Pearce's 23-man squad for England U21s' European Championship campaign. His first appearance for the side came as a substitute in the 2–2 draw with Italy U21s on 14 June 2007. Vaughan went on to make four appearances for the U21s between 2007 and 2011 with his record standing at one win, two draws and a loss, his final appearance for the U21s came in February 2011 against the same team he made his debut, Italy.
In September 2009, Vaughan joined Football League Championship club Derby County on a three-month loan.
On 8 September 2010, Vaughan joined Crystal Palace, the club against which he had become the Premier League's youngest goal-scorer, on a three-month loan deal. At the end of the loan spell he returned to Everton but, in January 2011, rejoined Palace until the end of the season. Vaughan made 30 appearances for Palace, scoring 9 times.
On 27 May 2011, Vaughan signed for newly promoted Premier League club Norwich City on a three-year contract for an undisclosed fee. Vaughan made his debut for the club against West Bromwich Albion on 11 September, and made a just five league appearances in an injury-hit first season.
In October 2012, Vaughan tweeted that he wanted to represent Jamaica at international level.
On 3 July 2013, Vaughan signed a three-year deal with Huddersfield for an undisclosed fee. He made his second debut for the club in the 1–0 defeat by Nottingham Forest on 3 August. After scoring two goals in the League Cup win over Bradford City on 6 August, he scored his first league goal on his return in the 1–1 draw with Queens Park Rangers on 10 August. On 24 August, he scored a hat-trick in a 5–1 win against A.F.C. Bournemouth.
Vaughan joined fellow Championship club Birmingham City on 26 November 2015, on loan until 2 January 2016. He made his debut as a second-half substitute in the next game, a 2–1 defeat at Brighton & Hove Albion, and made six appearances in total without scoring. The loan was then extended until the end of the season, when his contract with Huddersfield expired, at which point it would be converted to a one-year permanent contract with an option for a further season. He missed a penalty in Birmingham's FA Cup loss to Premier League club Bournemouth that would have given his side a lead, and finished the season with no goals from 16 appearances, most of which were as a substitute. During the close season, he was strongly linked with a move to Rangers, but no such move took place. He had been frustrated by his lack of first-team involvement in the second half of 2015–16 season, and when this continued into the new season – his only appearance was a start in the League Cup defeat to Oxford United – he chose to leave.
On 24 August 2016, Vaughan left Birmingham by mutual consent. He signed a two-year contract with Bury of League One. He made a scoring debut three days later away to Walsall, with Bury's second goal as they came back from 3–0 down to secure a draw. During the 2016–17 season Vaughan scored 24 goals, which earned him a place in the League One Team of the Year and made a major contribution to Bury narrowly avoiding relegation on the final day of the season.
On 13 July 2017, Vaughan joined Championship club Sunderland for an undisclosed fee reported to be around £500,000, reuniting him with former Huddersfield manager Simon Grayson. He scored his first goal for Sunderland in a 1–1 draw at Hull City on 16 September 2017.
On 12 January 2018, Vaughan signed for Wigan Athletic on an 18-month contract for an undisclosed fee, returning to League One after only scoring twice in 27 appearances for Sunderland.
