The UK Labour leader made a clear pitch for the centre ground as he addressed the Scottish Labour conference in Glasgow.
In a reference to the party's leftward shift under Jeremy Corbyn, he told activists: "Running away from the mainstream is running away from voters."
Sir Keir insisted Boris Johnson weakens the UK union "every day that he remains in power".
In his first speech to a Scottish party conference, Sir Keir said his government would be founded on "a new contract with the people".
He pointed to Labour’s commission on the UK’s future, which is being led by former prime minister Gordon Brown.
This will "create a new blueprint for a new Britain", putting security, prosperity and respect "at the heart of our politics again".
Sir Keir said: "Let me be clear, that means respect for Scotland within our union.
"That’s why Gordon’s commission is so important because it is examining how to reform the UK.
"Not just to acknowledge or accommodate devolution, but to give it proper respect and unleash the true power of the idea."
Sir Keir said Scottish votes "have never carried more weight in a general election", adding: "Those who pretend that Scotland can’t choose the government it gets are wrong.
"I understand the scale of the task that [Scottish Labour leader Anas Sarwar] and I have, but I’ve never taken on any job because I thought it was going to be easy."
The Labour leader was applauded as he quoted former prime minister Tony Blair and signalled a clear shift away from the Corbyn years.
He said: "We can win and we can make change or we can pursue apparent political purity inside this party. But please make no mistake, we cannot do both.”
He added: "Our party will continue to change, and I won’t apologise for that.
"Tony Blair said the only Labour tradition he’d wanted to change was losing - too right."
A spokeswoman for the Scottish Conservatives said Labour have lost votes in every Holyrood election.
She said: “No matter how much they try to gain support by appealing to nationalist voters, the Labour party is now mere a shadow of what it used to be.”
Earlier, Scottish Labour’s deputy leader Jackie Baillie told a conference fringe meeting that her party was “wrong” to have been part of the Better Together campaign during the 2014 independence referendum.
She said it should instead have run a “distinctive campaign”, separate from the Conservatives, and would do so in future if another vote took place.
She said: “We have been telling everybody for years that the Tories were terrible, and we cooperated with them.
"Don't get me wrong, there was a greater issue at stake, which was the future of the United Kingdom, but I think we were wrong to have done that.”
Ms Baillie said the SNP narrative about civic nationalism was “rubbish”.
She added: "The Labour Party hall in Dumbarton was torched. It burned down during that referendum. There was graffiti put up about killing people who voted a particular way during that referendum.
"My own car window was stoned and shattered during that referendum.”