Fortin, 40, will sit as an Independent until the 2015 federal election.
"The Bloc Quebecois in which I believed, which we believed, no longer exists," he said in a statement.
"The arrival of new leader Mario Beaulieu, who is pushing a one-dimensional, unrigorous and uncompromising approach, has put an end to the credibility established by Gilles Duceppe and continued by Daniel Paille, two leaders who deserved great respect."
After a summer of reflection, Fortin said he believes his constituents would be better served if he completed his mandate outside the party, which will now have only three MPs.
Beaulieu has made no bones about focusing on the promotion of sovereignty — an approach that differs from that of his predecessors.
Beaulieu, who is on a provincewide tour to drum up support for independence, has accused Duceppe and Paille of having a defeatist attitude with regard to sovereignty.
Fortin has represented Haute-Gaspesie-La Mitis-Matane-Matapedia since 2011. A political scientist and former municipal politician, he did not indicate if he would seek re-election next year.
Fortin says Beaulieu has radicalized the party with his dogmatic approach.
"It is not by rejecting those who seem less 'pure' and abandoning the rigour which has always characterized the Bloc in favour of repeating old...formulas that he will convince Quebecers to follow him,” Fortin said.
"This is not the way to serve Quebecers or advance sovereignty. In behaving this way, Mr. Beaulieu is dividing sovereigntists instead of uniting them."
His departure leaves leadership runner-up Andre Bellavance, Claude Patry and Louis Plamondon as the party's only MPs.
The Bloc has been in turmoil since its staggering defeat at the polls in 2011, when it was reduced to four seats from 47.
Fortin ran for the party leadership in 2011 and lost to Paille.
The runner-up in that race, Maria Mourani, was expelled from the Bloc caucus in September 2013 by Paille for criticizing the Parti Quebecois's now-defunct proposed charter of values.
She has since been sitting as an Independent and has denounced sovereignty.
Paille quit as leader in December 2013 because of health reasons, with Beaulieu replacing him this past June.