Appointed last year, this was former Holland boss Wiegman's first game at the helm, with a number of wasted chances the only complaint she could have as the Lionnesses outclassed their visitors to win 8-0.
England had waited 804 days for a competitive fixture but this was one by name only as they breezed to victory - Ellen White and Beth England helping themselves to braces with Ella Toone and Beth Mead on target and two own goals further widening the gap.
With North Macedonia sitting some 123 places below England in the FIFA rankings, this was never likely to be a close contest and the scoreline should have been even bigger but for some profligate finishing in front of 8,214 fans on the south coast.
Mead's low cross was steered just wide of the post by White as England predictably started on the front foot.
Toone - picking up her third cap after an impressive start to the WSL season at Manchester United - could only head wide when picked out free 10 yards from goal.
She would make amends just moments later, latching onto a perfect through ball from Leah Williamson and hitting a weak shot which somehow beat Suarta Dervishi in the visitors' goal.
Lauren Hemp was the next to miss a good chance, heading wide from six yards out having peeled away to the back post.
Toone's evening looked to be over as she went down in tears following an innocuous challenge but she was thankfully back on the pitch to help England finally double their lead.
She was involved in the build-up, keeping the ball alive before Macedonian defender Sara Kolarovska slid in and accidentally directed the ball into the path of White, who made no mistake.
Further calamitous defending allowed England to go in at half-time three goals to the good, Dervishi coming off her line and missing her attempt at punching clear a Mead corner, with Julija Zivikj then turning into her own goal.
Dervishi saved a Georgia Stanway drive with her feet as White next failed to connect with a fine Toone ball into the box before heading over another good chance.
Wiegman introduced Arsenal pair Lotte Wubben-Moy and Nikita Parris just after the hour, moments before the fourth goal was scored.
Captain for the night Williamson was tripped outside the box by the unfortunate Zivikj but referee Maria Madrona pointed for a penalty, with White converting her second of the night.
Jill Scott rattled the crossbar having come off the bench before fellow substitute England struck, heading home from point-blank range after Dervishi could only paw a cross-cum-shot from Parris into the forward's path.
Moments later and Kolarovska was next to turn into her own net, getting all tied up by a Mead cross and converting past Dervishi.
Parris missed a couple of chances to extend the lead before England headed home in the last minute and Mead got in on the act to complete the rout.