Brennan Johnson, on as a half-time substitute, and Richarlison both scored, while Timo Werner made goals for Destiny Udogie and Johnson as Spurs turned the game on its head in a 10-minute blitz at the start of the second half.
Ange Postecoglou's side has desperately struggled for cutting edge since Son left for the Asian Cup with South Korea, drawing a first blank in 10 months in Friday's defeat to Manchester City in the FA Cup and needing a late wonder goal to see off Burnley in the previous round.
For the first 45 minutes against the Bees, it was a similar story as the visitors laid out a blueprint for how to play against Spurs.
They packed the penalty area, forcing Spurs to play to play through a sea of shirts or go wide, and went direct to exploit the space behind the hosts' high line.
Without Son, there was no-one in white who could make something out of nothing and the closest Spurs came in the first half was when Richarlison did his best impression of the Korean by curling a well-struck effort a fraction wide of the post from 25 yards.
Too many Spurs players looked off it, including Destiny Udogie and Cristian Romero who were at fault for Brentford's opening goal, with the left-back losing the ball in the build-up and Romero too slow to react before Neal Maupay's fortuitous finish.
Spurs looked rattled by half-time, with Maupay acting as chief wind-up merchant, and they presumably had a rocket from Postecoglou in the dressing room. He introduced Johnson and Pierre-Emile Hojbjerg for Oliver Skipp and Rodrigo Bentancur for the restart.
The result was an instant transformation, with Werner playing in Udogie, who finished after his first effort was blocked, before the German crossed for Johnson to slide in at the back post.
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It felt like a big moment for both of the wingers, potentially lift-off for Werner in his second spell in England and perhaps a turning point for Johnson, who has been short of confidence and end product in a run of 11 games without a goal.
Though Brentford finished the game in the ascendency after Udogie had gifted Ivan Toney a goal, Werner and Johnson were both more confident in the second half, expressing themselves as Spurs looked for a fourth with some quick passing around the box.
Richarlison had rounded off Spurs' scoring with another poacher's finish after James Maddison's shot was blocked, making it seven goals as many Premier League games. The Brazilian also tested Mark Flekken in the Brentford goal late on.
There are doubts over whether Richarlison is a sharp enough finisher to be the long-term answer at centre-forward for Spurs but he is looking sharp right now, holding the ball up well and scoring. What more can you ask for?
This game might have been about Maddison's return or been another occasion defined by Son's absence. Instead, it was an important night for Spurs' other forwards, all of whom can look ahead to the second half of the season with more belief.