Hoffenheim’s on-loan Burnley frontman, whose winner in Dublin in September left Ireland with a mountain to climb, repeated the dose in Amsterdam to secure a 1-0 victory which was far more comprehensive than the scoreline suggested.
As a result, the Dutch secured second place in Group B behind France, who put 14 without reply past Gibraltar.
Stephen Kenny’s men, who have now won only six of the 29 competitive games they have played under his charge, barely laid a glove on a far superior side under the closed roof at the Johan Cruyff Arena on a night when they had hoped to bloody the nose of one of Europe’s traditional big guns.
Their feint hopes of securing a play-off berth via the Nations League were formally dashed on Thursday night by Slovakia’s 4-2 victory over Iceland with automatic qualification having slipped from their grasp long before.
Kenny is out of contract after Tuesday night’s friendly against New Zealand at the Aviva Stadium, with his future due to be resolved when the results of a review are presented to the Football Association of Ireland’s board on November 28, although few are expecting an extension.
Callum Robinson, making his first competitive start for his country since June last year, made an early impression with an inviting fifth-minute through-ball to Alan Browne, but although the midfielder struck his shot well he directed it straight at goalkeeper Bart Verbruggen.
Xavi Simons was less accurate at the other end as the Dutch mounted their first real attack, but they went ahead with just 12 minutes gone after Weghorst’s clever turn on to Stefan de Vrij’s pass on halfway left Nathan Collins for dead.
The striker sprinted upfield before smashing a rising shot past helpless keeper Gavin Bazunu and into the roof of the net.
The visitors’ efforts to work their way back into the game were repeatedly thwarted by a lack of penetration despite periods of possession and a tendency to surrender the ball in vulnerable positions.
As Liverpool frontman Cody Gakpo started to unfold his repertoire, aided and abetted by Xavi Simons, Ireland looked increasingly stretched.
The home defence, expertly marshalled by Virgil van Dijk, proved watertight as Ireland probed without reward, although the Netherlands failed to take advantage of their superiority at the other end with Gakpo and Tijjani Reijnders both missing the target from distance in quick succession.
Ireland were in disarray as the whistle approached, with Gakpo and Simons repeatedly carving them open, but they somehow made it to the break without further damage – thanks in part to Bazunu’s 44th-minute save from Reijnders.
They were fortunate not to fall further behind within three minutes when Simons connected with Denzel Dumfries’ cross at the end of a flowing counter-attack, only to see his goal-bound effort blocked by unwitting team-mate Gakpo.
Bazunu came to the rescue twice within seconds, first palming away Weghorst’s instinctive strike and then turning Reijnders’ dipping effort on to the post, prompting Kenny to replace the isolated Ferguson with midfielder Jamie McGrath.
Adam Idah thought he had levelled with 59 minutes gone when he ran on to Ryan Manning’s through-ball and cut inside Van Dijk before firing in a shot which clipped the defender’s heels and squirmed through Verbruggen’s legs and across the line, although the keeper’s blushes were spared by a late offside flag.
The Dutch swarmed all over the visitors in their pursuit for further goals, but lacked the necessary precision to prosper and ultimately found themselves under unnecessary pressure as the clock ticked down.