On Tuesday, congress voted to remove his immunity from prosecution amid corruption allegations.
Prosecutors accuse the president of masterminding a scheme to defraud the customs service of millions of dollars, allegations he denies.
A judge has barred Mr Perez Molina from leaving the country.
The president, whose term runs out in January, will now be summoned to appear before a court.
The detention order was signed by judge Miguel Angel Galvez, the prosecutor's office said.
A spokesman for Mr Perez Molina had earlier said the president would be "very respectful and submit himself to the rule of law".
On Tuesday, all members of congress present at the vote endorsed a move to strip the president of his immunity.
They included members of the president's own party.
A previous vote to remove his immunity failed last month.
But since then, more details of the corruption scandal have emerged and calls for the president to resign have increased.
Analysis: Katy Watson, BBC News
This would have been unthinkable just a few months ago. But so much has changed and Guatemalans feel empowered by what's happening with their country's politics.
Mr Perez Molina has repeatedly denied the allegations, and despite calls for him to step down, he has so far refused to listen.
His lawyer says he is prepared to face the accusations against him. Now with an arrest warrant, Guatemalans angry over government corruption are a step closer to seeing that happen.
Investigators allege that government officials received a cut from bribes paid by businesses seeking to evade import duties.
Vice-President Roxana Baldetti and a string of top officials have been forced to resign over the scandal.
Ms Baldetti is in jail awaiting trial on charges of taking millions of dollars in bribes.
The president was stripped of his immunity just days before presidential elections on Sunday.
Some protesters have demanded that the polls be postponed, but officials argue that it would be against the law.
Mr Otto Perez Molina is barred by the constitution from standing again.
An arrest warrant has been issued against Guatemala's President Otto Perez Molina, according to the public prosecutor's office.