Addressing a busy Downing Street on Tuesday morning, Mr Johnson said: "This is it, folks!"
He added that he would be offering “fervent support” to Liz Truss’ Government during a “tough time” for households across the country.
He said: “This is it, folks. Thank you everybody for coming out so early this morning. In only a couple of hours I will be in Balmoral to see Her Majesty the Queen and the torch will finally be passed to a new Conservative leader.
“The baton will be handed over in what has unexpectedly turned out to be a relay race. They changed the rules halfway through, but never mind that now.”
MPs and loyalists of the outgoing PM lined the streets in a show of support for the ousted leader of the Conservative Party.
Mr Johnson made a clear effort to celebrate "getting Brexit done" and the success of the vaccine rollout in his address.
He said: “Through that lacquered black door, a new prime minister will shortly go to meet a fantastic group of public servants.
“The people who got Brexit done. The people who delivered the fastest vaccine rollout in Europe, and never forget 70 percent of the entire population got a dose within six months – faster than any comparable country.
Boris Johnson making his last Downing Street speech as PM
Stefan Rousseau
Nadine Dorries, a known loyalist of Boris Johnson, with his sister Rachel Johnson
Yui Mok
Boris Johnson with his wife Carrie outside No.10
Aaron Chown
"That is government for you. That’s this Conservative government.”
Tory MPs who had gathered to the farewell speech, broke into cheers as he finished his address.
Mr Johnson held his wife’s hand and shook hands with officials as he left the street to rapturous applause.
He will travel to Balmoral later on Tuesday, to formally tender his resignation to the Queen.
Ms Truss will take over from Mr Johnson on Tuesday afternoon, and she will also make the trip to the Queen's Highlands home.
The Queen has opted not to travel back to London for the customary Buckingham Palace address with the Prime Minister in waiting.
Her Majesty will hold an audience with the new Tory leader, where Ms Truss will be invited to form a government and take over as PM.
It comes after weeks of sometimes bitter in-fighting among allies of the ex-Foreign Secretary and former Chancellor Rishi Sunak.
Ms Truss won the leadership race with 81,326 votes from the party membership, compared to Mr Sunak’s 60,399.
She said it was an "honour" to be announced as the winner, after a “hard-fought campaign” against Mr Sunak.
Ms Truss added: “I also want to thank our outgoing leader, my friend, Boris Johnson.
“Boris, you got Brexit done, you crushed Jeremy Corbyn, you rolled out the vaccine and you stood up to Vladimir Putin. You were admired from Kyiv to Carlisle.”
Liz Truss is taking over from Boris Johnson as leader of the Conservative Party
HANNAH MCKAY
Rishi Sunak was defeated in the race to take over from Boris Johnson
PA
After her meeting with the Queen, Ms Truss will return to Westminster where she is expected to address the nation for the first time as PM before getting down to the business of appointing her ministerial team.
The weather could result in her addressing the nation inside No 10 rather than outside the Downing Street door, as is tradition.
A number of key allies and supporters have already been pencilled in for some of the most senior roles, including Business Secretary Kwasi Kwarteng who is widely expected to be given the crucial role of Chancellor.
If confirmed he will have the task of delivering on her promised “bold” plan to deal with surging energy bills which have plunged households and businesses into crisis.
