Tottenham looked in danger of succumbing to a European giant-killing act when Stephen Rice put the Irish champions ahead after 50 minutes of average work by the Premier League side.
But Roman Pavlyuchenko's towering header opened the way for goals from Jermain Defoe and Giovani dos Santos in five frantic minutes as Tottenham made their superior class pay to eventually run out comfortable winners.
With the London derby against Arsenal on Sunday in mind Tottenham made 10 changes from the side which beat Wigan on Saturday.
Yet while Tottenham manager Harry Redknapp included youngsters such as Kyle Walker, Jake Livermore and Thomas Carroll in the starting line-up he still paid Rovers due respect with Defoe back from illness, Aaron Lennon returning from injury and experienced campaigners such as Sebastien Bassong, Vedran Corluka and Pavlyuchenko in the side.
As for Rovers they had not met an English team in a competitive European game since they became the first Irish side to feature in the European Cup in 1957-58 when they lost 6-0 at home against Manchester United and 3-2 in the return leg at Old Trafford, just months before the Munich air crash.
That was the history. The present Rovers side were determined to prove they could live with Premier League opposition and they made a pretty good fist of it in the first half with Rice and Stephen O'Donnell pressing and harrying in midfield and Gary Twigg working tirelessly up front.
Even so Tottenham should have taken the lead in the 17th minute when Defoe was put clear by an astute pass from Dos Santos, only for Rovers goalkeeper Richard Brush to touch the England striker's right-foot shot on to the crossbar.
Brush was in action again three minutes later, this time producing a smart, instinctive save when he blocked a close-range effort from Pavlyuchenko.
There was plenty of huff and puff from Tottenham, just a lack of accuracy with the final pass.
And while the travelling Irish fans cheered their side's every pass it was Tottenham who rattled the woodwork again just after the half hour when the lively Dos Santos played in Danny Rose whose shot cannoned off the crossbar.
Luck of the Irish, perhaps but there is more to Rovers' European journey than fortune. It had taken grit and resolve and no little skill to become the first Irish side to reach the group stages of either of the top two European competitions, including beating Partizan Belgrade in the play-off round last month.
Even so it was still a shock when in the 50th minute Rovers took the lead. A brilliant free-kick from Gary McCabe was palmed away by Tottenham goalkeeper Carlo Cudicini but Patrick Sullivan fired in the rebound and in the penalty melee which ensued Rice prodded the ball into the net.
Rovers 1-0 up and one of the great European shocks was on the cards.
Or at least it was until Tottenham woke up as the clock clicked on to the hour mark.
The impressive Dos Santos supplied the delivery and Pavlyuchenko rose high above the Irish defenders to head home. It was the Russian's first goal of the season and the relief was palpable around White Hart lane.
Cue a Tottenham surge with Defoe heading home a cross from substitute Andros Townsend two minutes later and Dos Santos making it five minutes of misery for Rovers when he smashed home his first goal for Tottenham since February 2009 with a powerful left-foot drive.
The Irish dream was over although you would hardly have known it such was the enduring and raucous support from their fans.
All that was left was for former Tottenham star Rohan Ricketts to come off the Rovers bench with 19 minutes remaining to savour a taste once more of life at the Lane and rue a night of what-might-have-beens.