The hosts took the lead in the 50th minute when Febian Brandy was tripped by Danny Holmes and Will Grigg notched his 18th of the season with a low drive from the subsequent penalty.
Seven minutes later a fantastic 30-yard shot from Craig Westcarr increased the Saddlers' lead and Tranmere rarely looked capable of saving a point.
Rovers had started brightly with Mamady Sidibie twice testing home 'keeper Aaron McCarey with low drives.
But Walsall's Jamie Paterson had a shot cleared off the line by Ash Taylor in the fifth minute and skipper Andy Butler headed straight into the hands of Rovers' keeper Owain Fon Williams when he should.
Both sides put the emphasis on attacking football and Paterson saw his 28th-minute volley well saved by Fon Williams before Saddlers midfielder Sam Mantom hit a post from 25 yards soon after.