Spain need a point from their match against Sweden this weekend to reach next year's World Cup finals after a 1-0 win in Greece put them in pole position in Group B qualifying.
A Pablo Sarabia penalty secured victory in Athens. The Sporting playmaker slotted home in the 26th minute after Inigo Martinez was tripped following a corner. Sarabia's low strike found the net to the left of Odysseas Vlachodimos.
In a nearly empty Athens Olympic Stadium, Spain dominated with 70% possession and were never in danger of losing.
"We knew that we only depended on ourselves to qualify to the World Cup. We won the first game and now we need to do the same on Sunday against Sweden. With the players that Spain have, it's an obligation to be in Qatar," captain Koke told reporters.
With nine players missing due to injury, Spain coach Luis Enrique surprisingly left Sergio Busquets, Jordi Alba and Cesar Azpilicueta out of his starting lineup.
Barcelona youngster Gavi did make the side and Espanyol forward Raul de Tomas was handed his debut in the absence of injured strikers Ferran Torres, Mikel Oyarzabal and Ansu Fati.
Spain's winner came after Dimitris Giannoulis fouled Inigo Martinez and Sarabia confidently converted the spot-kick.
Spain comfortably protected their lead in the second half as Greece struggled to create any clearcut chances.
After Sweden’s surprise 2-0 defeat in Georgia, Spain lead Group B with 16 points, one ahead of the Swedes who they host on Sunday in their final group match.
Sweden must beat Spain in Seville to qualify automatically for Qatar 2022 while a draw would be enough for the Spanish to progress. The runners-up will head into the playoffs in March.