Even when Scotland were down to 13 men in the first period - Andrew Mower and Simon Taylor were sin-binned in quick succession - they could not press home the advantage.
But they opened up after the interval as the visitors ran out of steam, running in tries through Ben Cohen and Jason Robinson (2) to end Scotland's brave resistance.
Full-back Josh Lewsey scored the first try of the afternoon - he was the beneficiary of some slick handling in the England backs which was concluded when he sprinted home virtually unchallenged.
Lewsey almost set up a second try in the 33rd minute when he slipped through the Scottish defence but with Robinson in support and unmarked, he was unable to get his pass away.
Northampton winger Cohen was hauled down inches short as the first-half neared its conclusion, but he could not be denied 10 minutes after the break when he pounced on a mistake by Bryan Redpath and dived over.
Robinson, who had been sin-binned in the first half for obstruction, showed the Scottish defence a clean pair of heals in the 63rd minute as he raced through under the posts.
The former Great Britain rugby league star then took a neat delayed pass from Matt Dawson to cross for his second.
Substitute Paul Grayson landed the conversion - Wilkinson had been substituted in the 66th minute - to complete the scoring and seal the Calcutta Cup.