The Catalan minnows' Ukrainian duo Artem Dovbyk and Viktor Tsygankov's goals helped Girona triumph from 2-1 down to move three points ahead of Real Madrid, who face Rayo Vallecano on Sunday.
Ivan Martin sent the visitors ahead but Osasuna striker Ante Budimir netted twice to turn the game on its head before Dovbyk and Tsygankov intervened and Aleix Garcia made the game safe in stoppage time.
Girona earned their 10th victory in 12 league games to continue their remarkable start to the season.
Martin netted the opener after a slick team move involving Savinho and Dovbyk, but Budimir pulled Osasuna level to ignite their El Sadar stadium.
There were no further goals in the end-to-end first half but Croatian target man Budimir nodded home early in the second period with a header after a 19-pass move.
Dovbyk headed home from Miguel Gutierrez' cross after 71 minutes to level the game, and then his compatriot Tsygankov struck at the second attempt after being teed up by the imposing striker.
Garcia rounded off the rout with a volley into the ground which bounced over Osasuna goalkeeper Sergio Herrera's dive.
Later Saturday champions Barcelona, fourth, visit fifth-place Real Sociedad.