The talks, to discuss peace process and prevent a Taliban resurgence when foreign troops withdraw from the war-torn country in 2014, featured top spy chiefs and military generals of the countries for the first time.
Speaking from his Chequers country retreat near London alongside Karzai and Zardari, Cameron also announced the opening of an office in the Qatari capital of Doha for negotiations between the Taliban and the Afghan High Peace Council.
Describing the trilateral summit with the leaders of Afghanistan and Pakistan as "an unprecedented level of cooperation", Cameron said "Now is the time for everyone to participate in a peaceful, political process in Afghanistan.
"This should lead to a future where all Afghans can participate peacefully in that country's political process".
The three leaders noted significant progress since they last met in September 2012 and stressed on the importance of maintaining the pace and momentum.
According to a statement issued by the British Prime Minister's office at 10 Downing Street here, President Zardari reiterated that Pakistan would extend "full support to peace and reconciliation" in Afghanistan.
It added: "The Afghan and Pakistani delegations agreed that the quality of dialogue and cooperation had significantly improved.
"Both sides agreed that good neighbourly relations between Afghanistan and Pakistan, that ensured the long term stability of both countries, was of fundamental importance".