About 200 gay campaigners gathered outside the cathedral were heckled by dozens of counter protesters, including a group of skinheads wearing dark blue uniforms and gloves who gave a Nazi salute.
Police and paramilitary gendarmes kept the two groups apart, as they shouted slogans at each other in a face off that lasted more than two hours.
An hour into the demonstration, around 10 gay couples staged their “kiss-in” to applause from their supporters and heckling from the counter-protesters.
“It is a victory against obscurantism and intolerance,” David Souvestre, president of Gay Pride Lyon, told reporters.
“But the presence of fundamentalists here, that was predictable,” he added.
Gay rights activists carried placards and banners including one declaring “Homophobia Kills. Free to love everywhere”.
Banners held by the Catholic counter-protesters including one that read: “We are the children of heteros, first, second, third generation”. Other Catholics dropped to their knees and said Hail Marys.
The demonstration had originally been scheduled for Saturday, International Day against Homophobia, but local officials postponed it despite the protests of the gay rights groups involved.