The first Evening Standard under George Osborne's editorship has focused on reported strained relations between the PM and the EU.
Under the front page headline "Brussels twists knife on Brexit, the paper's political editor says the European Parliament's chief Brexit negotiator has openly mocked Theresa May.
Former Chancellor Mr Osborne backed Remain in the referendum.
He had pledged to be "fearless" and "independent" in his new role.
As he arrived for his first day, Mr Osborne - the Conservative MP for Tatton - said: "It's very exciting to be starting in the new job.
"It's a really important time in our country when people are going to want the straight facts, the informed analysis so they can make the really big decisions about this country's future."
He also tweeted at the end of the day, sharing a photograph of himself with an Evening Standard employee and thanking the team for "all the help today".
His appointment at the Standard in March provoked accusations he was juggling too many responsibilities, as he was still an MP and had recently taken on a £650,000-a-year position as an advisor to US investment company Blackrock.
He was sacked as chancellor last July after Mrs May became prime minister and later announced he would not be standing as an MP in the June general election.
The Advisory Committee on Business Appointments has imposed a two-year ban on Mr Osborne lobbying former ministerial colleagues on behalf of his new employers, and stopped him from discussing the issue of press regulation with the government.
The Standard's front page article by Joe Murphy refers to reports of disagreements over the Brexit negotiations at a private dinner between Mrs May and the president of the European Commission, Jean-Claude Juncker, last week.
It notes that No 10 attempted to keep out of the row, quoting the prime minister's spokesman as saying: "We approach these talks with all parties in a constructive manner and with a huge amount of goodwill."
Elsewhere, in a leading article, the Standard says it respects the democratic decision of the people who voted to leave the EU "even though it continues to believe it to be an historic mistake".
It said reports of Mrs May's dinner with Mr Juncker - said to have come via European Commission sources - show "how unrealistic were the claims made about the strength of Britain's hand".
The paper says it is committed to "optimism, freedom, diversity and enterprise" and "will argue for a Britain that doesn't retreat within itself but remains engaged in Europe and the world".
It says: "We will be the voice of London on issues from air quality to knife crime - as we are today - but we won't restrict ourselves to issues that primarily affect the capital."
The paper carries news of an exclusive poll which suggests nearly seven in 10 people do not believe the prime minister will meet her pledge to cut net immigration to below 100,000.
There is also a comment piece by Thomas Hetherwick, the designer of the Thames Garden Bridge, which last week lost the support of the mayor of London.
The bridge across the river had been championed by Mr Osborne as chancellor.
The Guardian's media writer Jane Martinson said Mr Osborne's first paper as editor demonstrated that he "intends to take on Theresa May".
Political blogger Guido Fawkes said the Standard's editorial "repeats the Juncker briefing uncritically as if it is gospel".
The BBC's political editor Laura Kuenssberg tweeted: "Irony alert - George Osborne's first editorial in Standard warns govt against only repeating slogans, and asking for a 'blank cheque'".