The embattled conservative leader, in power since 2012, took the decision to step down to confront “individually the proceedings against him,” his spokesman Jorge Ortega said, hours after the arrest warrant was issued.
New Vice President Alejandro Maldonado is due to assume power, ahead of a general election on Sunday during which voters will choose a new president to take office in 2016.
Perez is accused of masterminding a huge fraud scheme, known as “La Linea” (The Line), a scandal that already forced his former vice president to step aside.
Six of his 14 ministers have resigned in recent days, along with several other top officials.
Perez is expected to appear before a judge Thursday and has reportedly agreed to cooperate with the investigation.
The 64-year-old was stripped of his immunity Tuesday by Congress, an unprecedented step in the country that was welcomed by many protesters.