More than 700 ministers, deacons and elders will meet in the capital to make decisions on Kirk policy and governance.
The week-long gathering will see the appointment of a new Moderator, Reverend Colin Sinclair, who succeeds the Rt Rev Susan Brown in the role.
First Minister Nicola Sturgeon is expected to attend the opening day before addressing the General Assembly on Wednesday.
Scottish Labour MSP Anas Sarwar has been invited to discuss Islamophobia at the Church's Heart & Soul festival in Princes Street Gardens on Sunday.
Over the course of the week commissioners will debate and vote on proposals to create a 12-person trustee body to hold responsibility for the Church's finances.
They will also be asked to consider plans to reduce administration costs by 20 to 30% and merge four of the Church's Councils into two.
Rev Dr George Whyte, Principal Clerk to the General Assembly, said: "This General Assembly will be asked to make bold plans for the future of the Church of Scotland.
"There will be proposals to invest in growth, to work in new ways and to put mission right at the top our priorities.
"If Commissioners accept the proposals the Church will see a radical shift of resources and energy towards the local church."
The Assembly was first held in 1560, the year of the Scottish Reformation, which marked the beginning of the Protestant Church of Scotland.
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