Educated at Oriel College, Oxford and the Paul H. Nitze School of Advanced International Studies of the Johns Hopkins University, he began his career as a civil servant in the Foreign and Commonwealth Office (FCO) in 1972. He has served in embassies in Poland, India, Paris, and Moscow, and within the FCO he has worked on the Central American desk, the Russian desk and held several senior positions. He has represented the UK in Brussels and also at the International Conference on the former Yugoslavia in 1994.
Between 1995 and 1998, he was British ambassador to Israel; from 2001, he was a foreign policy adviser to British Prime Minister Tony Blair. During this time he developed a close relationship with his counterpart, then US National Security Advisor Condoleezza Rice. Blair selected him to replace Christopher Meyer as the British Ambassador to the United States. Manning took up the post in 2003.
His close relationship with the Prime Minister suggests he has been a key figure in driving British foreign policy in respect of the United States, particularly in the aftermath of the September 11, 2001 attacks and the decision to invade Iraq.