In stark contrast from their drab 0-0 draw at the Deutsche Bank Park last week, the two sides put on a much more entertaining spectacle, during which Daichi Kamada opened the scoring for Die Adler.
However, two strikes from Son Heung-min either side of a Harry Kane penalty turned the tide in the Lilywhites' favour before half time, and Frankfurt could not spark a miraculous turnaround after Faride Alidou's late consolation.
Antonio Conte reverted to a 3-4-3 system for the visit of the Europa League champions, but the home crowd was silenced within the opening 15 minutes following a calamitous mistake from Eric Dier.
The England centre-back took a heavy touch inside his own area, which allowed Jesper Lindstrom to steal in and feed the ball into the centre, where Hugo Lloris managed to palm it away from the lurking Randal Kolo Muani.
Despite Lloris's best efforts, the ball fell kindly into the path of Sebastien Rode, who unselfishly laid off Kamada for the Japanese playmaker to find the back of the net once again in London.
Frankfurt's advantage lasted all of six minutes, though, as Kane and Son combined for the 50th time in all competitions for the latter to curl home the equaliser past Kevin Trapp.
The Lilywhites demonstrated a cutting edge that was totally non-existent in Germany last week, and with 28 minutes on the clock, Kristijan Jakic clumsily bundled over Kane in the area.
Referee Carlos del Cerro Grande initially waved away the protests, but he awarded a penalty after a quick look at the monitor, and Trapp could not stop Kane's spot kick despite diving the right way.
Tottenham experienced plenty of joy in the space left occupied by Frankfurt's wing-backs, and the Premier League side made it three in emphatic fashion on the 35-minute mark.
Some nifty footwork from Pierre-Emile Hojbjerg on the right-hand side opened up space for the Danish midfielder to cross, and Son was left unmarked in acres of space to connect with a thunderous left-footed volley into the roof of the net.
Oliver Glasner's half-time team talk proved ineffective for Frankfurt, and any hopes of Die Adler clawing their way back into the contest were virtually extinguished when Tuta was given his marching orders.
The 23-year-old had only been booked a few minutes before hauling down Son, and after a brief period of uncertainty, the referee brandished the red card as Frankfurt went down to 10 men.
Tottenham were seemingly on their way to a comfortable win as the game entered its dying embers, but hearts were in mouths when substitute Alidou rose highest to head home from a corner in the 87th minute and set up a nail-biting finale.
However, it was Spurs who were presented with a gilt-edged chance to restore their two-goal lead when Hrvoje Smolcic tripped substitute Bryan Gil in the box, but Kane could not replicate his previous spot-kick success as he blazed over from 12 yards.
Tottenham managed to ride out that chaotic end to the game to pick up all three points, which has seen them usurp Sporting Lisbon at the top of Group D with seven points after the Portuguese side went down 2-0 to Marseille.
Conte's side are only one point clear at the summit, but they could seal qualification for the last-16 with victory over Sporting on October 26, while Frankfurt have dropped to fourth place.