The 22-year-old Dynamo Kiev player had not long been thrown into the fray by coach Andriy Shevchenko when he latched onto Andriy Yarmolenko’s superb through ball and fired past an exposed David de Gea in the 76th minute.
The goal came against the run of play with Spain applying most of the pressure at the Olympic Stadium, where coronavirus restrictions were eased enough to allow a limited number of fans to attend.
It was a shock result after Spain — who had not lost since November 2018 — won 4-0 when the sides met in Madrid just last month, and Ukraine are now only a point behind Luis Enrique’s team in League A, Group 4.
With two rounds of matches still to play in November, Spain top the group on seven points, a point above both Germany and Ukraine, with winless Switzerland bottom on just two points.
Germany came from 2-0 and then 3-2 down to draw 3-3 with the Swiss in Cologne on Tuesday.
The Ukraine squad had been hit by a host of coronavirus cases before being trounced 7-1 by France in a friendly in Paris last week, and Andriy Shevchenko’s side then lost 2-1 at home to Germany at the weekend.
They were fortunate not to fall behind on several occasions against Spain, with goalkeeper Georgiy Bushchan doing well to tip over a Rodrigo Moreno header early on.
Bushchan, of Dynamo Kiev, also tipped over a Sergio Ramos free-kick in the first half, while Manchester City midfielder Rodri hit the post in the 65th minute.
Luis Enrique sent on Ferran Torres along with Mikel Oyarzabal, the Real Sociedad forward who scored in the 1-0 win over Switzerland at the weekend, but Spain could not find a way through.
It was a disappointing return for them to the stadium where they beat Italy 4-0 in the final of Euro 2012, and Spain have managed just one goal in three outings this month.
Often criticised for his performances with Manchester United, De Gea will also face scrutiny for his positioning at the goal, and Spain’s home meeting with Germany next month is shaping up to be decisive in deciding who advances to the four-team finals.