US General John Campbell made the comments at a ceremony in Kabul to mark the end of NATO's combat mission.
From New Year's Day, the US led International Security and Assistance Force will be replaced by a training and support mission, called Resolute Support.
The ISAF Commander, United States General John Campbell, describes the moment as the end of one era, and the start of a new one.
"A 13-year endeavour filled with significant achievements and tremendous sacrifice, especially by the thousands of coalition and Afghan army and police wounded and fallen who gave so much to build a brighter future for this war-torn land."
Afghan National Security Advisor, Mohammad Anif Atmar paid tribute to the sacrifices made since 2001.
"On behalf of President Ghani and the people of Afghanistan, I would like to express our deepest gratitude for the NATO coalition's efforts and sacrifices in Afghanistan since 2001. The costs of our struggle have been enormous."
The NATO Afghan deployment began after the September 11 attacks in the US and, at its peak, involved more than 130,000 people from 50 countries.
Since 2002, 42 Australians have been killed while serving in the country; 41 with Australian Defence Forces and one with the British Armed Forces.
And after more than a decade of fighting, the Taliban is still active and appears to be gaining in strength.
The past 12 months has been the bloodiest since 2001.
They're facts the ISAF commanders are well aware of as the mission ends its combat role and begins a new training and support mission, with about 12,000 troops staying in the country.
Lieutenant General Carsten Jacobson is ISAF's Deputy Commander says the new mission isn't a straightforward one.
"It is a non-combat mission in a combat environment. A combat environment means that we are still facing an insurgency that is fighting against our Afghan friends and brothers in arms and that will also put challenges against us so we have to be prepared to defend ourselves but it is a non-combat mission."
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