Speaking at a news conference in China, she made her first public comments on the arrest last week of a 31-year-old man suspected of spying for the US.
German prosecutors say the man is suspected of handing over more than 200 documents between 2012 and 2014.
It has been reported he was an employee of Germany's foreign intelligence service who says he sold his services to the US.
At a news conference in Beijing, Mrs Merkel said: "If the allegations are true, it would be for me a clear contradiction as to what I consider to be trusting co-operation between agencies and partners."
Germany has been stepping up pressure on the US to clarify the situation. The issue threatens to strain German-US relations again after earlier reports the National Security Agency spied on Germans, including on Mrs Merkel's cellphone.
German interior minister Thomas de Maiziere is said to want to include the US among future German spy targets in response to the case.
Foreign Minister Frank-Walter Steinmeier said if the allegations of US involvement were true, the case could lead to unspecified changes in the two countries' "daily routine".
He added: "Should the suspicions be confirmed that American intelligence agencies were involved, then that's also a political matter where one can't just go back to the daily routine.
"We will work hard to answer the outstanding questions and then decide how to react. I hope the US can contribute to resolving this matter as quickly as possible."
In Berlin on her book tour, former US secretary of state Hillary Clinton said the US would never sign a commitment with any other nation not to spy on them.
She added: "But that doesn't mean the two countries shouldn't clarify what's appropriate and what isn't."