"I love the president and wish him well," Dowd told NBC News.
Dowd's resignation comes only two days after he told CNBC "No" when asked whether Trump would be soon making changes to his legal team, as The New York Times had reported Monday.
The Times, which also broke the news of Dowd's departure, noted that he had been considering leaving in recent months, after having been tapped to head Trump's legal team last summer.
Dowd thought that Trump was increasingly ignoring his legal advice, the Times said, citing a person briefed on Dowd's departure.
Specifically, Dowd opposed Trump's desire to be interviewed by Mueller's office.
In a statement after Dowd's resignation announcement, another Trump lawyer, Jay Sekulow, said: "We will continue our ongoing representation of the President and our cooperation with the Office of Special Counsel."
He added: "John Dowd is a friend and has been a valuable member of our legal team."
Two sources close to the president's legal team told NBC News that Trump is interested in bringing back his previous lead lawyer for the Russia probe, Marc Kasowitz, who was removed last summer.
Kasowitz, who is currently representing Trump in a defamation lawsuit filed in New York state court by an ex-"Apprentice" contestant who claims Trump sexually groped her, "is someone the president can trust" as he grows anxious about the Mueller probe, according to NBC News.
Last weekend, Dowd called on Deputy Attorney General Rod Rosenstein, who has oversight over the Russian probe because of Attorney General Jeff Session's recusal, to end that investigation by Mueller's office.
The Times reported that Trump was angry that Dowd, who had originally claimed to be speaking on the president's behalf in that call, had backtracked by claiming he was actually not speaking for Trump.