Hibs did not have it all their own way as Ben Williams twice made sharp saves, either side of Griffiths hitting the post, before a sumptuous strike from Kenny McLean put Saints ahead after 32 minutes.
Griffiths netted the equaliser after 37 minutes, scored his second after 65 minutes and Jim Goodwin was sent off for two bookable offences two minutes later as a fourth home win this term took Hibs top for 24 hours at least, until Celtic play Dundee United.
On this form Griffiths, the SPL top scorer with 11, could be included in the Scotland squad, whether Craig Levein is manager or not, on Tuesday.
First place may be Hibs' fleetingly, but is a mark of their improvement since Pat Fenlon's appointment as manager almost a year ago, particularly this season and at home, where Hibs are unbeaten this term.
The Buddies, meanwhile, are a warning of what can happen in a congested SPL table should Hibs' standards slip.
Four successive losses and 11 goals conceded have seen Saints fall from fourth to 11th in a month, with only Dundee below them.
Fenlon made one enforced change from the somewhat fortuitous, but nevertheless impressive, 4-0 Friday night win at Motherwell, with right-back Tim Clancy (groin) replaced by Alan Maybury.
St Mirren, buoyed by the League Cup quarter-final penalty shootout victory at Aberdeen and seeking a first SPL win since September, went close after 14 minutes when Sam Parkin and Steven Thompson combined in a crowded penalty area, the latter's low shot saved by Williams.
But Fenlon's Hibs are now resilient, a quality not seen at Easter Road in two-and-a-half years of struggle and one required to thwart the visitors, who regularly looked to Dougie Imrie and McLean to create on the left.
Also present is a clinical finisher in Griffiths. The striker, on-loan from Wolves, exploited a mix-up between Goodwin and Marc McAusland to cut in on the left side of the box and hit the inside of the post, only to see the ball bounce out.
Goodwin was booked soon after for a foul on Ryan McGivern before Saints went on the attack.
Thompson lifted the ball over for McLean to shoot low and Williams made a sharp save.
It was a warning Hibs failed to heed as the hosts dithered over a corner which they had opportunities to clear and Saints took the lead.
Tom Taiwo was twice culpable, his second attempt a weak header which fell for McLean, who took a touch before firing left-footed into the bottom corner from 30 yards.
Hibs' resilience returned and they responded quickly when Paul Cairney's cross drifted to the far post and Griffiths, who had time to pick his spot.
Cairney fired wide early in the second period before Taiwo tried to pass when he should have shot after being played in by David Wotherspoon.
Hibs took the lead when lively duo Wotherspoon and Cairney combined before Griffiths made space for himself on his favoured left foot and drilled low into the goal.
Saints' troubles deepened when Goodwin was dismissed for a second bookable offence following an altercation with Wotherspoon, leaving the visitors short-handed for the remaining 23 minutes.
Referee Alan Muir was informed of the incident by David Watt, his assistant, and Goodwin's protestations were in vain.
Griffiths, searching for his hat-trick, struck a post with a 25-yard free-kick and found the net in the 86th minute, only to be found offside.
Thompson was denied late on by Williams, who along with Griffiths was a standout performer as Hibs celebrated going top of the table.