Chief Secretary to the Treasury Danny Alexander, former Lib Dem leader Charles Kennedy and John Thurso were beaten by the SNP.
The turnout for the constituencies involved exceeded 70%.
The SNP's Angus MacNeil held his seat in Na h-Eileanan an Iar  - which covers the Western Isles - with 54% of the votes.
Mr Kennedy, who lost Ross, Skye and Lochaber to Ian Blackford, said the 2015 election's defeat of Lib Dems and Labour in Scotland would become known as the "night of the long sgian dubhs".
The former Lib Dem leader said: "I am very fond of political history and tonight, if nothing else, we can all consider and reflect in years to come, and perhaps tell our grandchildren, we were there the night of the long sgian dubhs."
His opponent Mr Blackford said the election in Scotland had not been about last year's referendum, but about "sending MPs from Scotland who will stand up for" Scotland's interests.
In Inverness, Nairn, Badenoch and Strathspey, Highland Council leader Drew Hendry gained almost 29,000 votes, a rise of more than 31% on the party's 2010 result to defeat Mr Alexander.
Mr Alexander said he had polled about as many votes as he had in 2010 but they had not been enough to get him re-elected.
He said the Liberal Democrats should hold their heads high for what they achieved in government, but conceded that "clearly we have a lot of rebuilding to do".
Mr Alexander added: "The flame of Highland liberalism will keep burning and our job is to burn brighter in years to come."
Lord Thurso lost Caithness, Sutherland and Easter Ross, a seat he had held since 2001, to the SNP's Paul Monaghan who won 46% of the vote.
The SNP's Mr MacNeil said his job now was to fight for the needs of the Western Isles and help his party's desire to end austerity.
High profile Liberal Democrats have lost three strongholds in the Highlands and Islands.