Mrs Merkel announced she wants Jean-Claude Juncker to get the key post despite the Prime Minister making clear he views the former Luxembourg leader as a symbol of Europe's past.
Mr Cameron was thought to have won over some of his counterparts at a Brussels summit this week, where he argued a reformer should take charge of the EU executive.
He insisted that recent elections, which saw strong performances by Eurosceptic parties across the continent, demonstrated the need for change.
But speaking at the National Catholic Congress in Regensburg, Mrs Merkel is reported to have said: "I will now lead all negotiations in the spirit that Jean-Claude Juncker should become president of the European commission."
Both Mrs Merkel and Mr Juncker's parties are members of the European People's party (EPP) bloc, which still dominates the parliament and has selected him as its preferred candidate.
However, previously she had stopped short of endorsing him for the job, saying "anything is possible".
Mr Cameron had earlier stressed the importance of securing a presidency contender focused on openness and flexibility instead of one bound up in the union's past.
Speaking on Tuesday, Mr Cameron said: "We need an approach that recognises that Brussels has got too big, too bossy, too interfering. We need more for nation states."