Cipriani joined Wasps Academy in 2003 and made his debut against Bristol aged 17 in December 2004 in the Powergen Cup. Cipriani joined the Wasps Academy full-time in the 2006–07 season. He initially played for Wasps under-21 team and Wasps A team before making more regular appearances for the first team in 2007. He started as Wasps won the 2007 Heineken Cup Final.

Cipriani was part of the Saxons’ side that won the Churchill Cup at Twickenham in 2007. He just missed out on selection for the 2007 Rugby World Cup for England, despite spending the summer in their training camp. He was called up to the England squad for the 2008 Six Nations Championship. Many experts were calling for Cipriani to be picked at full-back to ease him into the international arena, a position he played successfully with Wasps upon breaking into the first team. His starting debut for England was due to be realised when he was picked at full-back for the game against Scotland on 8 March 2008. However, two days before Cipriani was to make his full England debut, he was axed from the squad due to “inappropriate behaviour”. Cipriani was photographed leaving a London nightclub at 12.30am.

On 6 October 2008 Cipriani was involved in a bust-up with club and international teammate Josh Lewsey in a training ground fight. Cipriani was left nursing a bloody nose and cut lip following the incident at Wasps’ training ground. The spat started after Lewsey accused Cipriani of missing several tackles during a full-contact session.

On 18 May 2008, Cipriani suffered a fracture dislocation of his right ankle during Wasps semi-final play-off victory over Bath. Cipriani was tackled by Olly Barkley and got trapped at the bottom of a ruck in the 49th minute at Adams Park. He was ruled out of England’s tour of New Zealand due to his ankle fracture. The injury also ruled him out of Wasps’ victory in the 2007–08 Premiership final.

Cipriani made his return to Wasps in a Premiership match against Bath on 1 October 2008. His recovery has been described as remarkable, given the severity of the injury, and because his return was six weeks to two months ahead of schedule. His sprint coach Margot Wells has been quoted as saying that due to Cipriani’s superb attitude and hard work, he will return ‘stronger in the tackle, fitter and faster than before’.

He started the match against Ireland on 15 March 2008, which England won 33–10, replacing Jonny Wilkinson at fly-half. He had a successful match, converting all of his goal kicks and controlling the game well.

Cipriani was named in the England Saxons squad on 1 July 2008. On his return to England he scored 19 points including a try. After a long period of time in international wilderness, Cipriani was called up to the 2014 England rugby union tour of New Zealand, coming off the bench in the 1st and 3rd tests. He was named on the bench for the opening match against Wales in the 2015 6nations but failed to make an appearance. The following week, he replaced George Ford during the second half against Italy and scored a try with his second touch. England went on to win 47–17.

Cipriani played his last home match for London Wasps on 1 May 2010 against Cardiff Blues in the Amlin Challenge Cup semi-final.

In February 2010, Wasps announced Cipriani would join the Melbourne Rebels. Rebels’ Coach Rod Macqueen said, “Danny Cipriani is … coming for all the right reasons. [He] is on the right path to the culture we are after.” In England, there was speculation about Cipriani’s chances of English selection for the 2011 Rugby World Cup. While England’s manager Martin Johnson said he would not select Cipriani if he moved to the southern hemisphere, former English international Austin Healey said he believed Cipriani could still feature for England at the tournament in New Zealand.

In August 2010 Neil Warnock, manager of the London-based football club Queens Park Rangers, revealed Cipriani would train with the Rangers and might even play for the reserves in preparation for his move to Melbourne. Cipriani also trained with London football club Tottenham Hotspur. In September 2010, Cipriani went to Denver to train with the Colorado Rapids, which he said was for “altitude training”. During September 2010 Cipriani trained with the Milton Keynes Dons and was reportedly offered the chance to sign with them if he did not enjoy his first season in Melbourne.

Despite issues with his Australian work visa, Cipriani joined the Rebels for pre-season training in late 2010. He trained at fly-half, and in early 2011 was one of two captains to lead the Rebels in two friendly trials against the visiting Tongans.

In the 2011 season he was criticised for his poor defence.

Cipriani signed a new three-year contract with Sale Sharks to join them at the beginning of the 2013–14 season. He has scored over 200 points, including four tries in the first four games of the 2012–13 LV= Cup, making him the second highest points scorer behind Harlequins’ Ben Botica, in this year he also helped Sale reach the LV= Cup Final, has scored a sensational try against Scarlets and, up to this point, been an integral part of Sale Sharks survival bid in this seasons Aviva Premiership. In May 2014 Cipriani was selected for England’s 30-man squad for the three-match tour to New Zealand in June.

In 2014, Cipriani posed shirtless for a PETA “Ink Not Mink” ad, showing off his tattoos on behalf of the anti-fur campaign.

Cipriani was arrested for drink-driving after the car he was driving was involved in a collision with a taxi at 05:15 on 1 June 2015. He was convicted after a five-day trial for drink-driving before Westminster Magistrates’ Court on 24 June 2016. He was ordered to pay a total of £7,620 in fines and costs and banned from driving for 18 months.

In February 2016 it was announced that Cipriani would rejoin the Wasps for the 2016–17 season. After two seasons with Wasps, Cipriani joined Gloucester Rugby for the 2018-19 season.

In 2016, Cipriani was left out of new coach Eddie Jones’ first elite player squad for the Six Nations.

On 15 August 2018, during a pre-season tour in Jersey, Cipriani was arrested after an incident at a nightclub in St Helier. He was charged with common assault on a doorman, larceny, assault on a police woman, resisting arrest and being disorderly on licensed premises later that day.

In May 2019 he was voted Player of the Year by the Rugby Players Association.

Cipriani dated television presenter Caroline Flack in 2019.

In February 2020, Cipriani revealed that he has suffered from depression since the age of 22.