It was a lacklustre performance all round for the much changed Spurs team and even four half-time substitutions could not prevent defeat in Belgium.
Royal Antwerp took the lead just 29 minutes into the first half after Dieumerci Mbokani robbed Ben Davies of possession and played in Lior Refaelov, who rifled home.
Spurs trailed at the break and Jose Mourinho was clearly unhappy with the way he was playing as he made four changes.
Dele Alli, Giovani Lo Celso, Steven Bergwijn and Vinicius all came off for Erik Lamela, Pierre-Emile Hojbjerg, Lucas Moura and Heung-min Son.
Tottenham improved after the break but in their search for a goal chances still came for Antwerp.
Mbokani had a glorious chance inside the six-yard box, ten minutes after half-time, but skied his effort over the bar. Replays suggested there may have been an offside in the build-up.
Mourinho had to call on Harry Kane in an effort to get something from the game as he replaced Gareth Bale, who struggled to have much of an impact.
Antwerp looked increasingly dangerous on the counter attack and Juklerod found himself in on goal in the 71st minute but blazed his effort over the bar.
Spurs had plenty of possession in the final stages of the match and chances fell the way of Kane and Son in the final stages but some last-ditch defending from Antwerp prevented them from finding an equaliser.
Gareth Bale is yet to get going in a Tottenham shirt and struggled as his side lost 1-0 to Antwerp in the Europa League.