Etherington's first-half double put the Potters in firm control at the Britannia Stadium.
But Spurs pulled a goal back via Emmanuel Adebayor's penalty only to see their hopes of a comeback undermined by Younes Kaboul's late red card.
It was Spurs' first Premier League defeat in 12 matches and London rivals Chelsea now have the opportunity to climb above them into third with victory over leaders Manchester City on Monday.
Victory for the Potters made it three consecutive wins in the English top flight as well as continuing their fine record against the big clubs in the Premier League this season, with Stoke having also beaten Liverpool and drawn with Manchester United and Chelsea.
Stoke manager Tony Pulis named an unchanged side which included the former Tottenham trio of Peter Crouch, Etherington and Jonathan Woodgate, while Spurs boss Harry Redknapp recalled Rafael van der Vaart in place of Jermain Defoe.
As so often at the Britannia, Stoke piled on the pressure straight from the whistle and took just 37 seconds to create their first opening.
With Rory Delap on the bench, it was left to Ryan Shotton to deliver one of those trademark Potters long throws.
Benoit Assou-Ekotto's attempted headed clearance fell straight to Etherington, whose stinging volley was palmed away by Brad Friedel, and Jonathan Walters could only find the side netting from the rebound.
Redknapp's team could barely escape their own half and there was an air of inevitablity about Stoke's 13th-minute opener.
Again Shotton was at the heart of it, as his deflected cross was flicked on by Walters for Crouch, who evaded William Gallas before crossing for Etherington to rifle home.
Spurs struggled badly to find their rhythm but Thomas Sorensen was fully extended by a swerving low strike by Luka Modric which the goalkeeper did well to turn around the post.
Spurs claimed they should have had a free-kick when Woodgate and Scott Parker collided on the edge of the Potters area and, already on a booking, the defender would have been relieved to see referee Chris Foy wave play on.
It was a key moment as two minutes before the interval Pulis's team doubled their advantage.
Once more Shotton was the creator as his long throw was nodded on by Walters and Etherington, having evaded marker Parker, bundled the ball beyond Friedel.
Redknapp responded by making two changes upon resumption, replacing Assou-Ekotto and Aaron Lennon with Sebastien Bassong and Defoe in a tactical reshuffle.
Spurs came within inches of scoring when Kyle Walker's inviting cross deflected off Woodgate and agonisingly past the far post.
Yet they halved the deficit in the 62nd minute when Adebayor converted from the penalty spot after Foy adjudged Whelan's outstretched leg toppled Modric inside the area despite Stoke's claims the Croatia international dived.
By now the momentum had firmly shifted in the visitors' favour and it took a fine save from Sorensen to tip a Parker drive over the crossbar.
Meanwhile Spurs' calls for a second penalty when Kaboul fell under pressure from Ryan Shawcross were rejected.
Luck did not appear to be on Spurs' side as Kaboul was denied on the line by Shawcross's arm before Adebayor slipped in the loose ball only for the goal to be wrongly ruled out for offside.
Tottenham's hopes were dealt a further blow when Kaboul received his second yellow card with eight minutes remaining for a clumsy foul on Walters and Stoke comfortably held on, even hitting the crossbar via Shawcross late on.
Source: AFP
Source: AFP