Ryan has had three number one hits while with Blue. He had previously co-directed the video for Blue’s single “Breathe Easy”, which he also wrote and which was shot in Prague. In 2001 the group were in New York during the September 11 attacks after which Ryan commented that “This New York thing is being blown out of proportion” and asked “What about whales? They are ignoring animals that are more important. Animals need saving and that’s more important.” The other members of the group tried to silence Ryan, but he went on. This caused a huge media backlash that resulted in Blue losing a record deal in the United States and campaigns to sack Ryan from the line up. In August 2003 Ryan was arrested and charged with driving with excess alcohol in central London. In May 2004 Ryan was cleared of assaulting two photographers who had attempted to take photos of him leaving a nightclub however he was convicted of criminal damage for smashing their cameras.

Ryan is a member of boy band Blue along with Simon Webbe, Duncan James and Antony Costa. The group has sold over 14 million records worldwide. In August 2005, Blue split up to pursue solo careers under the advice of Sir Elton John. Blue reformed on 28 April 2009.

Ryan released his first single “Army of Lovers” on 18 July 2005. It debuted at No. 3 in the UK Singles Chart and hit No. 1 in Italy. On 1 August 2005, Ryan released his debut album, Lee Ryan, to mixed reviews. The album reached No. 6 in the UK Album Chart and No. 3 in Italy. “Turn Your Car Around” was the second single lifted from the album which had moderate success. In January 2006, Ryan released his third and final single in the UK “When I Think of You”. The song reached No. 15 in the UK. “Real Love” was used for the end credits of the film Ice Age: The Meltdown which later led to Ryan voicing the part of an elk in the UK version of the film and Eddie in the Italian version. In late 2005, Dolce & Gabbana signed Ryan up to be the UK face of their new line of clothing.

After the relative success of his first solo album, Ryan started planning his second solo album. The single “Reinforce Love” was released on 10 December 2007. The single was being released for Great Ormond Street Hospital and CLIC Sargent, which were the two charities that Ryan was touring for in November and December 2007, with young voices. The album was then postponed, and finally cancelled. He appeared in the video for the single “Red Light” by a British girlband named Fe-Nix. In September 2007, he appeared as one of the contestants in Hell’s Kitchen. However he rowed with Marco Pierre White about White’s use of the term “pikey”, and subsequently left the show. In August and September 2008, Ryan acted alongside Natalie Casey in The Pretender Agenda at The New Players Theatre in London. In June 2008 Ryan was found guilty of assaulting a taxi driver in Oxted and ordered to pay compensation to the victim.

In March 2010, Ryan confirmed that he had signed a new record deal with Geffen Records, due to last until 2013. Later that month, it was announced that Ryan’s first album on his new record label, Confessions, was due to be released in October 2010. The first single from the album, “Secret Love”, was released as a double A-Side with “I Am Who I Am” on 4 July 2010. The single peaked at number 33 on the UK Singles Chart. Following this, it was announced that Geffen were set to drop Ryan from the label, before work on his album had been completed. Ryan announced in January 2011 that there was no deal to release his album.

The track listing for Ryan’s aborted album was as follows: “Secret Love”, “I Am Who I Am”, “Guardian Angel”, “Perfect Strangers”, “I Don’t Wanna Let You Down”, “I Love Your Smile”, “It’s Not Me”, “Confessions”, “Light of Your Soul”, “Peaches”, “Reinforce Love”, “Suffice to Say”, “To See the Stars”, “Stop the Rain”, “Why Me” and “Stand Up as People”. In August 2010 Ryan was charged with assaulting his former fiancée however these charges were officially withdrawn.

Ryan stated in January 2011 that he was working on an album with Blue to be released later in the year. Blue represented the United Kingdom at the Eurovision Song Contest 2011 in Düsseldorf, Germany with the song “I Can”, placing 11th overall.

In 2013, Blue released “Hurt Lovers” the first single from their fourth album Roulette.

In August 2013, Ryan and Duncan James appeared in an episode of comedy panel show Through the Keyhole in which the host showed around their home in London.

Ryan appeared in Celebrity Big Brother 13 in 2014. Following the show he entered a relationship with fellow Big Brother participant Jasmine Waltz. Waltz split with Ryan a few weeks later claiming on Twitter that Ryan had cheated on her with a man. Ryan came out as bisexual during his time on Big Brother, later stating in an interview, “I’m very open about what I’ve done in the past but that was the easiest way to come out. I did so much other stuff that people didn’t even notice.”

In May 2014 Ryan pleaded guilty to criminal damage and failing to provide a specimen after being caught driving erratically in April.

In November 2014, Blue announced they had signed a two-album record deal with Sony Music. The band released their fifth studio album Colours on 9 March 2015. He was in Strictly Come Dancing 2019, but went out in the third round.

On 15 February 2017, it was confirmed that Ryan had landed a role in the BBC soap opera, EastEnders. He was cast as Woody Woodward, initially for a short stint between 18 April and 19 May. It was later announced that Woody would be promoted to a regular role and that Ryan had signed a one-year contract with the show. He later received 2017 Inside Soap Award nomination for Best Newcomer.

In 2019 he was a candidate in the seventh season of the British reality TV-show Celebs Go Dating. From September to November 2019 Lee Ryan went on a UK-Tour with the musical “Rip it Up the 70s”.

When discussing sexuality and dating on Good Morning Britain in August 2019, Ryan was asked if he had dated men, to which he replied, “Yeah, I think a lot of people are a lot more liberal which is great for our society. I mean we aren’t living in the Dark Ages any more and for people to have some kind of prejudice against these kinds of things is just ignorant”.