The Rocky actor tied the knot with his third wife in 1997, and the pair share three children together.
Their romance was the subject of intense speculation recently after the 76-year-old covered up a tattoo tribute to Jennifer with a portrait of beloved dog Butkus, from the boxing franchise.
According to reports, she has since submitted paperwork on Friday in Florida, requesting to end their marriage.
The reason behind their split has not been confirmed.
A rep shared a message with TMZ from the Expendables actor, who said: ‘I love my family. We are amicably and privately addressing these personal issues.’
The publication reports that she asked to restore her maiden name of Flavin, and requested to keep their home in Palm Beach while proceedings are ongoing.
Sylvester and Jennifer tied the knot in 1997 and recently celebrated their 25-year anniversary on social media.
‘Happy 25th anniversary to my amazing wife,’ the Expendables star said at the time.
‘There are not enough words to describe what this incredibly selfless dedicated, patient, woman has meant to our lives and I only wish they could be another 25! Thank you, sweetheart!’
However, their marriage attracted scrutiny this month when Sly covered up an inking dedicated to his wife on his bicep – with a design of Butkus.
A rep later shut down any speculation, telling MailOnline: ‘Mr. Stallone intended to refresh the tattoo image of his wife Jennifer however the results were unsatisfactory and, unfortunately, unfixable.
‘As a result, he had to cover the original image with a tattoo of his dog from Rocky, Butkus.
Source: Metro UK