First Minister Alex Salmond joined hundreds of marchers in calling for the Trident nuclear programme to be scrapped.
Police estimated about 1,000 people gathered in Edinburgh for the Cut Trident Not Jobs march organised by anti-nuclear campaigners.
Mr Salmond, joined by trade union and Church of Scotland representatives, appealed to the UK Government to drop multi-billion pound plans to replace the Trident nuclear submarine system currently based at Faslane on the Clyde.
Mr Salmond described the costs involved as "indefensible and obscene" and said Trident would be a central issue in the forthcoming general election campaign.
Addressing the rally, he said: "There is massive opposition to dumping a new generation of weapons of mass destruction in Scotland. The Scottish Parliament has voted against the 'son of Trident', a majority of Scottish MPs reject it, and it is going to be a central issue in the general election campaign.
"At a time when Westminster is imposing cuts in public services to deal with Labour's recession, with much deeper cuts planned in the future, and the Scottish Government's budget is falling in real terms for the first time since devolution, to waste £100billion on weapons of mass destruction is indefensible and obscene.
"Any way you look at it - on moral, financial, or defence grounds - renewal of Trident is completely untenable, and I believe that position can prevail in the general election.
"The tide has well and truly turned on Trident - and the general election offers the opportunity to ensure that weapons of mass destruction are banished from Scotland forever."
Westminster plans to update and replace Trident were narrowly approved by MPs in 2007.
The proposal, which would cost around £20billion, has been opposed by some senior former members of the armed forces.
Organisers of the Edinburgh event said money spent on Trident would be at the expense of public sector jobs and services in Scotland, and that rather than defending the UK, having a nuclear arsenal made it a target.
The march began outside the Scottish Parliament and travelled along the Royal Mile towards the Grassmarket, where speeches were made.
Reverend Ian Galloway, CND chairman Kate Hudson and actor David Hayman, all took part in the protest.
Mr Galloway, convener of the Church and Society Council of the Church of Scotland, said: "I do this out of a firmly-held personal conviction that nuclear weapons are wrong as they kill indiscriminately, but also because the Church of Scotland has long spoken out against such weapons."