The sixth series was commissioned by Jane Tranter, Head of Drama Commissioning at the BBC, by the time series 5 was announced. The series returned on 16 October 2007 at 9 pm on BBC One, and concluded on 18 December. The series averaged 5.68 million viewers (the lowest to date.) The sixth series was markedly different from the previous 5. For the first time, end credits were broadcast and there was less frequent use of the soundtrack composed by Jennie Muskett. The sixth series also attempted to weave a common strand across all ten episodes - the efforts of the MI5 and the British Government to strike a peace deal with the Iranian Government, having been tricked into bombing a chemical weapons train in Tehran by American intelligence. While the US prepared a pre-emptive war against Iran, MI5 attempted to maintain the peace and cover up the evidence of the UK train attack from both the public and Iran. Complicating these matters was Adam Carter's affair with the UK Iranian Ambassador's wife. During the course of the series, the serial arc was moved into and out of individual episodes.

The series ended on a cliff-hanger. Jo and Adam, captured by a terrorist group offering spies to the highest bidder, faced torture and eventual death, the group also being responsible for the torture and death of Zaf who disappeared after the Tehran bombing. Jo asked Adam to kill her rather than let her face a similar end. The final scene was of CO19 Specialist Firearms Command mounting a rescue by breaking into the house in which they are held captive, just as a limp Jo is shown in the arms of a devastated Adam.

A new website, Spooks Interactive, was published to coincide with the launch. In April 2008, the Spooks production team won the BAFTA Award for Interactivity for their work on Spooks Interactive.