He told the French news agency AFP that their "shared life" had now ended.
The announcement came just hours after Hollande's office at the Elysee Palace dispelled any notion that the couple were to split.
A spokesperson said: "There will be no announcement today. They are false rumours circulating in the French media."
Hollande told reporters he was speaking in a personal capacity and not as the head of state.
He said: "I am making it known that I have put an end to my shared life with Valerie Trierweiler."
Hollande has never denied having a long-running affair with French actress Julie Gayet.
Earlier in the week, he admitted he was having a "difficult moment" in his relationship with Trierweiler but insisted the matter was to remain private.
Two weeks ago, celebrity magazine Closer published photos apparently showing a nocturnal tryst between Hollande and Gayet.Trierweiler spent a week in hospital in the wake of the public revelations, while Gayet announced that she is suing Closer magazine for breach of privacy.
On Thursday, Trierweiler fired her lawyer after he said she was looking to end her relationship "with the greatest possible dignity".
Trierweiler has left hospital and has been staying at an official residence, La Lanterne, near Versailles.
She is expected to travel to India today in support of the work of the French charity Action Against Hunger.
Speaking to the newspaper Le Parisien, a member of Trierweiler's entourage said: "He [Hollande] has consulted her and brought her up to date, she accepts the situation as a fait accompli, but she is leaving it to him to take the initiative."
The relationship between the president and Trierweiler first began in November 2007.
The announcement came six months after the French president had left his previous partner, one-time French presidential candidate Segolene Royal, with whom he has four children. Although they have never married, Trierweiler became the unofficial first lady of France - the country has no such position like America - in May 2012, after Hollande's victory in the presidential election.
In its expose, Closer magazine said that the affair between Hollande and Gayet had started during the 2012 presidential race.
The strength of the French presidency is being questioned as Hollande's political agenda continues to take a back seat.
The president has promised to reinvigorate the French economy which has struggled in the face of high unemployment. But recent press conferences called to detail his fiscal plans were swamped with questions relating to his private life.
Friday's visit to Rome to meet the pope was also overshadowed by concerns of his personal indiscretions, despite the fact the president refused to take questions.
A French poll also showed that two-thirds of people surveyed believed that the focus on his alleged affair had been bad for the image of the country.
Public opinion has not been kind to Hollande as the 59-year-old is considered to be the most unpopular president in modern France, according to another poll.