After performing in several pirate radio stations during his late teens, Green signed a record deal with The Beats in 2006, releasing his debut mixtape, Lecture #1. He rose to mainstream prominence after supporting Lily Allen on her 2008 concert tour.
He released his debut album, Alive Till I'm Dead, on 19 July 2010, which debuted at number two on the UK Albums Chart. The album was certified gold by the British Phonographic Industry. Green's second album, At Your Inconvenience, was released on 25 October 2011 and also reached number two in the UK. The album was also certified gold by the BPI.
Green's third album, Growing Up in Public, was released on 2 September 2013 and debuted at number three on the UK Albums Chart. The album was certified silver by the BPI. In 2015, Green released his fourth album, The System Is Over. The album peaked at number 20 on the UK Albums Chart.
In addition to his music career, Green has also appeared as a coach on the BBC television show The Voice UK and as a host on the ITV2 reality show Take Me Out. He has also written a book, Professor Green: Lucky.
In 2022, Green revealed that he had been diagnosed with ADHD and OCD, and that he had been struggling with his mental health for many years. He has spoken openly about his experiences in an effort to raise awareness of mental health issues and to help others who may be struggling.
Green has also been involved in several charitable endeavours. He is an ambassador for the mental health charity CALM (Campaign Against Living Miserably), and he has also worked with the charities Oxfam and Save the Children.