Denham returned to government in 2007 as a Member of Prime Minister Gordon Brown's Cabinet, which he served in until Labour's election defeat in 2010.

Denham announced in 2011 that he would be standing down from Parliament at the next election, and held his final front bench position as Parliamentary private secretary to Miliband from 2011 to 2013.

John Denham was born in Seaton, Devon, and attended Woodroffe School in Lyme Regis, Dorset, and the University of Southampton, where he was awarded a Bachelor of Science degree in Chemistry, and served as president of the students' union in the academic year 1976–77.

He was selected to contest the Southampton Itchen seat at the 1983 general election following the defection to the Social Democratic Party of the sitting Labour MP Bob Mitchell.

The election proved to be a close-run affair, with Denham coming in third place, Mitchell in second, and the victor was the Conservative Christopher Chope who gained the seat with a majority of 5,290.

Denham made his maiden speech on 20 May 1992, reminding people that the Pilgrim Fathers left from Southampton, and not Plymouth as is widely thought, on their historic voyage to North America.

[citation needed] Following Brown's installation as Prime Minister in June 2007, Denham was named to take over the new post of Secretary of State for Innovation, Universities and Skills.

[citation needed] In an interview with the Daily Telegraph, Denham stated that he was a secular humanist, although he also said he learnt a lot from his Church of England upbringing.