In a letter, made public on his Twitter account, Finance Secretary Carlos Manuel Urzúa Macías said there were many economic “discrepancies”.
He also said in the letter that economic policy had to be based on evidence and be free of “extremism”.
The currency and stock markets fell after the news of his resignation.
Arturo Herrera Gutiérrez has taken over as finance secretary of Latin America’s second-largest economy.
“There were many discrepancies in economic matters,” Mr Urzúa wrote in the letter addressed to the country’s president dated 9 July.
“I am convinced that all economic policy should be carried out based on evidence, taking care of the different effects it can have and free from all extremism, be it from the right or left.”
He also found “the imposition of officials without knowledge of public finances” to be “unacceptable”.
‘Uncertainty to persist’
Mr Herrera told his first news conference since being named finance minister that he did not see an impending recession, according to Reuters. Mexico’s economy shrank 0.2% in the first quarter of 2019 from the previous quarter.
Mr López Obrador came into power on a promise to carry out “radical transformation” of his country and to deliver economic growth, jobs and social development programmes.
While the appointment of Mr Herrerra, a government official recognized for his technical capacity, would appease some investors, Moody’s ratings agency said, concerns about Mexico’s economy would continue.
“We expect investor uncertainty with regards to economic policy management to persist. This is in line with the views that led us to assign a negative outlook on Mexico’s sovereign rating earlier this year,” said Moody’s Vice President Jaime Reusche in a statement.