The Greek international headed home to seal a famous win for the Scottish champions - who ended a losing run of 11 successive away Champions League losses since drawing in Barcelona in 2004 - and complete a great second-half comeback.
That had been sparked when trailing 2-1 - thanks to an Emmanuel Emmenike double - French referee Tony Chapron sent off Spartak defender Juan Insaurralde just after the hour mark for bringing down Gary Hooper, who had given Celtic the lead early in the first-half.
Celtic - whose last away win in the European Cup came in 1986 over Irish side Shamrock Rovers - broke the deadlock with their first attack of the match after they had been pegged back by the hosts for the opening 10 minutes.
Victor Wanyama won the ball with a brilliant tackle in midfield and the Kenyan star fed Swedish international Mikael Lustig out on the left, who beat a defender before putting in a perfect low cross for Hooper to put it away into the far corner.
Hooper - scoring his 60th goal in 99 games for Celtic since moving from unglamorous English side Scunthorpe - had the ball in the back of the net again in the 24th minute but he had just veered offside when he met Samaras's cross.
Celtic suffered a blow subsequently when Wanyama picked up a booking which rules him out of the daunting trip to Barcelona in their next Group game.
Spartak, though, deservedly levelled before the break as another brilliant long pass by Kim Kallstrom found Brazilian Ari, who passed the ball inside to Emenike and he made no mistake planting the ball past Fraser Forster.
Celtic got off to the worst possible start to the second-half as Ari and Emenike combined for the second goal, though, a large part of the blame has to go to Forster.
Emenike's shot from outside the box looked to be going wide, after taking a deflection off Kelvin Wilson, but Forster opted to save it, only managing to tip it to Ari, whose unselfish pass inside found Emenike and he tapped into an empty net.
The match swung back Celtic's way when Charpon, after consulting his assistant, sent off Insaurralde.
Celtic manager Neil Lennon made an inspired substitution soon after, taking off Wanyama and sending on James Forrest whose first shot on goal after a good move by the visitors was saved by the Spartak 'keeper but it rebounded in off defender Dmitri Kombarov in the 71st minute.
Source: AFP
Source: AFP