Ashton’s position at Wigan Warriors was normally fullback, although he also played on the wing. He came through Wigan’s scholarship programme and played for Wigan’s U18s in 2003. He made his senior début in Wigan’s last match of the 2005 season, and scored two of their seven tries in a 36–22 victory over Huddersfield Giants.

Although some criticisms were made about his defensive abilities, he earned a call into the England squad at the end of 2006 while Great Britain were on tour in Australia and New Zealand. Ashton made his England début against France on 22 October 2006 in the Federation Shield tournament. He played in all four Federation Shield matches, which concluded with England winning the competition, and he scored three tries in his four games.

On 19 March 2007 it was announced that Ashton had signed to play rugby union for Northampton Saints, after Wigan granted him an early release from his contract.

On 1 September 2007, he made his début for Northampton at Franklin’s Gardens as a late substitute for Will Harries against London Welsh in National Division One. He scored his first try for the club, with his first touch of the ball, in the same game which Saints won 44–11.

In 2008, Ashton broke the National Division One try scoring record, scoring 39 tries (and one conversion) from only 25 appearances.

He made his England début against France on 20 March 2010 in Paris. He played left wing, the opposite side to his usual position with Northampton. He gave the scoring pass to fellow Saints player fullback Ben Foden, who was also making his first Six Nations start.

He was taken on the summer tour to Australia, and played in both Test matches. Although England lost the first Test, they won the second 20–21. Ashton scored his first international try in this match. On 13 November 2010, England defeated Australia at Twickenham. Ashton was the hero of the match with two tries in a 35–18 victory, the second after a run from inside the England’s 22-metre line.

Ashton scored two tries in England’s opening match in the 2011 Six Nations against Wales at the Millennium Stadium on 4 February, with England winning the game 26–19. He followed this with four tries against Italy the following week, equalling the all-time Six Nations record with six tries in a season. This performance also meant he is the first person in the Six Nations to score four tries in a single match. His famous swallow dive celebration was used to celebrate two of these tries.

On 19 January 2012, it was announced that Ashton had signed with Saracens, and joined up with his new team for the start of the 2012–13 season.

Ashton’s Saracens contract was rumoured to be worth £250,000 per season. On 1 September 2012, he made his Saracens début against London Irish. He scored two tries on his début, in a game which Saracens won 40–3.

He started all five matches for England in the 2012 Six Nations, and in May 2012 scored a hat-trick of tries as England beat the Barbarians 57–26 in a non-cap fixture at Twickenham. Ashton went on the 2012 summer tour to South Africa in which he started all three Test matches.

Ashton started all five matches for England in the 2013 Six Nations Championship, scoring a try in the first match against Scotland. England took the championship down to the final game against Wales, however suffered a heavy 30–3 defeat at the Millennium Stadium as Wales took the title. Ashton later played in all three of England’s matches in the 2013 autumn internationals, scoring a try in their win over Argentina.

Ashton lost his place in the England elite squad, not playing in any of their games in the 2014 Six Nations. He did however play in England’s mid-year games against the All Blacks in New Zealand, all three of which England lost. Again, Ashton’s defensive capabilities were the subject of much discussion during this campaign and he did not play for England during the 2014 autumn internationals or 2015 Six Nations.

Ashton received a 10-week ban in 2016 for eye-gouging; an appeal against the ban was dismissed. In September 2016 Ashton received a 13-week ban for biting Saints’ Alex Waller in a premiership match on 17 September. He was free to play again on 19 December.

In October 2016, Ashton signed for French club Toulon in the Top 14 from the 2017–18 season. Ashton played a single season in the Top 14, scoring 24 tries in 23 appearances to break the tryscoring record previously held by Napolioni Nalaga.

Ashton’s decision to join Toulon in October 2016 appeared to end his hopes of an England recall, as he would not be eligible for selection by playing outside England.

On 3 July 2018 it was confirmed that Ashton was to return to England when he signed for Sale Sharks from the 2018–19 season.

However, he returned to England with Sale next year, notably after winning a game against England with the Barbarians at Twickenham in May 2018, scoring a hat trick in a performance that saw England conceding a record points total at Twickenham. This game might have brought Ashton much closer to coming back in Eddie Jones’ squad.

Later in 2018, despite being banned for seven weeks for a tip tackle in August 2018, was selected in the England squad for the Autumn internationals. In November 2018, Ashton made his first England appearance in four years, coming off the bench in their 12–11 win over South Africa, before being named in the starting fifteen against New Zealand.

He left the club by mutual consent on 2 March 2020.

On 4 March 2020, after his contract was terminated by Sale Sharks, Ashton signed for Harlequins. Head of rugby Paul Gustard described him as “without doubt one of the most competitive, professional and dedicated athletes” he had come across.