Chacón, Spain's Minister for Defence in the socialist government of José Luis Rodríguez Zapatero, made the announcement on Thursday.
She will now teach Comparative Public Law and International Politics at Miami Dade College.
During a press conference to explain her decision, Chacón said she was leaving her seat "but not politics".
"I'm leaving with a return ticket," said the politician who was tipped by many for the PSOE's top job but narrowly missed out in February 2012 to current socialist leader Alfredo Pérez Rubalcaba.
On Thursday, Chacón also took a sideswipe at the PSOE, a party which was failed to reclaim ground since crashing out of office in Spain's general elections in late 2011.
"I had a project of generational change and I presented it to the PSOE a year and a half ago," Chacón said of her failed attempt to become the party's General Secretary.
"I'm convinced that this project of political and generational renewal remains in force, and not just for Spanish socialism but for the whole party system," she said.
"Things have to happen in my party, and they have to happen as soon as possible," she added.
Chacón will be back in Spain briefly in November to take part in the PSOE's national conference.