Barca made two changes from their disappointing draw at home to Athletic Bilbao over the weekend, with Arthur and Phillipe Coutinho in the starting eleven.
Spurs welcomed back goalkeeper Hugo Lloris from injury, but still missed a host of key players such as Christian Eriksen and Dele Alli.
The visitors wasted no time stamping their authority after taking the lead as early as the second minute through the boot of Coutinho after a cut back from Jordi Alba.
Spurs began to settle after going down, but Barca were in no mood to let them off the hook by any stretch of the imagination.
Their first chance propped up on 25 minutes when Harry Kane shot from distance but the ball bounced into the ground and arms of Marc-Andre Ter Stegen.
The Spaniards took advantage of their carelessness as Ivan Rakitic thumped home the second from outside the box to put them in firm control.
Tottenham were shell shocked and threatened a response when Erik Lamela’s run down the right saw his shot deflected off the defence, with the ball nearly propping in at the far post.
On the other side, the Catalans eased through the game with power and control of every angle of the big Wembley surface with the half drawing to a close.
The second half resumed with neither side making changes but sticking with the individuals that started the first period.
Talisman Lionel Messi came forth for Barca to get them a third but was twoce denied by the back off the post in five minutes.
Spurs pulled one back courtesy of Kane who finished off an incisive counterattack with a bottom corner strike on 52 minutes.
The joy and thought of a come back was short-lived as Messi stepped forward to reinstill their two-goal advantage seconds later.
Spurs made their first substitution. Eric Dier replaced Victor Wanyama to keep their slim hopes of a come back alive.
The Londoners did manage to pull back another goal after a deflected shot from Lamela trickled off Clement Lenglet and into the net on 66 minutes.
Spurs made their second change. Moussa Sissoko for Heung-Min Son, while Barca made two changes with Rafinha and Arturo Vidal late on in the game.
It got worse for Spurs when Messi rounded off the victory in added time with a nice finish to maintain Barca’s fine start to the tournament in Group B.