Italy striker Scamacca, David Moyes’ marquee summer signing from Sassuolo, netted a first-half header on his full debut with the Irons taking a two-goal lead to Denmark for the second leg of their Europa Conference League play-off.
It gave the Hammers some breathing space ahead of the second leg of this qualifying play-off in Denmark next week as they bid to make the group stages of the Europa Conference League.
West Ham were without Declan Rice and Aaron Cresswell, as well as Moyes, with all banned for various indiscretions in the agonising Europa League semi-final defeat to Eintracht Frankfurt in May.
It had also been a tough build-up for Viborg for what was probably the biggest night in their history after two players, Nigerian winger Ibrahim Said and Gambia forward Alassana Jatta, were denied entry into the country due to visa rules post-Brexit.
Nevertheless, burly striker Jay-Roy Grot was proving a handful up front for the visitors, especially for stand-in Hammers skipper Angelo Ogbonna who was making his first appearance in nine months after a cruciate injury.
Areola was forced into a flying save from Nils Mortimer to prevent the Danes from drawing level before Antonio scored the third with tap-in from fellow sub Said Benrahma’s pull-back.