Manchester United drew 2-2 in Lyon following Rayan Cherki's stoppage-time equaliser for the hosts after substitute Joshua Zirkzee thought he had won it for the English.
Thiago Almada's free-kick bounced in to give Lyon the lead and Leny Yoro's clever header had brought the 2017 winners level just before the break.
Athletic Bilbao, who host May's final, drew 0-0 at 10-man Rangers. The Scots had Robin Pröpper sent off after just 13 minutes for bringing down Nico Williams and the Basques thought they had taken the led through Alex Berenguer in the 76th minute.
But video reviews chalked off the goal and awarded a penalty to Bilbao instead, which Berenguer then missed.
Frankfurt, the 2022 Europa League winners who are third in the Bundesliga this term, will confidently go into next Thursday's home leg against Spurs thanks to Ekitiké's brilliance.
The French striker cut inside and fired an unstoppable low shot into the corner from just outside the area after just six minutes.
The Londoners, down in 14th in the Premier League after an injury-hit and inconsistant season, levelled through Porro's clever flick from James Madison's cross on 26.
The fans inside the futuristic Tottenham Hotspur Stadium responded with a spine-tingling atmosphere as Ange Postecoglou's men pushed but Frankfurt clung on for the draw.
Earlier, Norwegian champions Bodø/Glimt beat Lazio 2-0 at home thanks to an Ulrik Saltnes double.
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