Goalkeeper Hugo Lloris and Ben Davies were the only survivors from the Spurs side that edged Burnley on Monday, but Gareth Bale started for the second time since re-joining.
Spurs enjoyed a bright spark in the opening minutes, with Steven Bergwijn, Harry Winks and Dele Alli firing at Antwerp goalkeeper Jean Butez from various angles.
Congolese-born Dieumerci Mbokani brought the hosts to life a minute to the half-hour mark with a low ball from the right spotting Lior Refaelov who took one touch to leave Lloris static.
Spurs looked to head into halftime all square through Bergwijn, while Antwerp nearly had a second from the same variation on the right but a timeous block from Davies sparred the visitors.
Heung-Min Son was one of four changes at the break, with Pierre-Emile Hojbjerg, Lucas Moura, Erik Lamela the others as Spurs went all out for the equaliser.
Mbokani had a golden chance to double their lead nine minutes from halftime following a ball across the six-yard area from Refaelov, but the forward blazed over with the goal in clear sight.
Son was brought into action on 62 minutes after landing onto a ball at the near post from the right-side by Moura, but the Korean had his path to goal blocked.
The LilyWhites were under siege again eight minutes later when a through ball from the middle sent Simen Juklerod clear, but the latter failed to profit.
Spurs still enjoyed a decent spell as the contest headed to the climax, however the lack of a killer touch up front led to their first Europa League group stage defeat this season.