Alex Younger – known as 'C' – said that in the past two years, the intelligence services had "disrupted multiple serious Daesh attack plans originating overseas that if successful would have caused significant loss of life".
In a speech at St Andrews University, he said: "This includes an important contribution to helping European countries, particularly our French and German allies, prevent terrorist attacks in their countries or against their citizens.
"This has involved exceptionally difficult and dangerous work. We have asked our agents – the people who agree to work in secret for MI6 – to do extraordinary things and run great risks. And I will not hide from you that some have paid the ultimate sacrifice.
"Our country and our allies owe them a debt that they can never truly know and never fully repay."
In a rare speech, Mr Younger said he was "proud" of MI6's contribution to helping destroy "the so-called Caliphate" in Syria, with a "welcome effect on the direct threat to Europe".
Referring to terror attacks including last year's Manchester atrocity, he said: "But to be clear, if the tragic events of 2017 in the UK are not a sufficient reminder, we face a persistent and evolving threat from terrorism, one that demands we evolve at every turn."
On Russia and the Salisbury nerve agent attack, he told how some adversaries – including Vladimir Putin's regime – "regard themselves as being in a perpetual state of confrontation with us".
He said: "We did not respond to this flagrant hostile attack by emulating Russian tactics.
"We operationalised our values, our legal system and alliances. We exposed the perpetrators and coordinated the largest ever collective expulsion of Russian intelligence officers from Nato and partner states, significantly degrading Russian intelligence capability."
Mr Younger said the intention was to make the Russian state "conclude that, whatever benefits it thinks it is accruing accruing from this activity, they are not worth the risk".
Asked if more should have been done to protect Sergei Skripal, he said: "I will never talk about whether someone was an agent of ours and I will not talk abut arrangements the Government put in place to resettle people.
He added: "But I will say that Mr Skripal came to the UK in an American brokered exchange having been pardoned by the president of Russian
"To the extent that we assumed that had meaning, we will not makes that assumption against."
He also told how Russia – which has denied the Salisbury attack, including by claiming the two agents were in the city on a sight-seeing trip – was operating using "misinformation", a "disguised use of force seen in Ukraine or elsewhere, combined with political obfuscation – or what you might call implausible deniability".
But appearing to reach out to Mr Putin, he said: "I should emphasise that even as the Russian state seeks to destabilise us, we do not do not seek to destabilise Russia. We do not seek an escalation. If we see a change in Russian behaviour, we will respond positively.
"But we will be implacable in defence of our people and our vital interests."
C also told how the increasingly complex "hybrid" warfare employed by enemies – including cyber attacks – raised questions about Article 5 of the Nato treaty, which states that an armed attack against one or more member countries will be considered an attack on all.
He said: "But it presupposes a clear distinction between a condition of war and a condition of peace – precisely the distinction that our opponents seeks to obscure.
"As allies are are determined to uphold and deepen our Article 5 commitment each other's security. But it is significant that face adversaries who now regard themselves as being in a perpetual state of confrontation with us."
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