Spain moved closer to securing a World Cup spot with a convincing 3-0 win Saturday over Italy after a remarkable performance by Real Madrid forward Francisco "Isco" Alarcon.
Gareth Bale's Wales got back in contention in its group thanks to a winner by 17-year-old striker Benjamin Woodburn five minutes into his international debut.
The result in Madrid ended Italy's 11-year, 56-game unbeaten run in all qualifiers, and extended Spain's own run without a loss in World Cup qualifying to 60 matches.
Serbia took the outright lead in Group D by beating Moldova 3-0, while Ukraine moved ahead in Group I by defeating Turkey 2-0.
Spain opened a three-point lead over Italy, taking control of the difficult Group G with three games left for each team.
"We played a very good match against a great rival," Spain coach Julen Lopetegui said. "We knew it was going to be difficult and the team responded well. We are happy with the result but we know that we haven't qualified yet. We have to do our job in the final three games."
Only the group winners automatically advance in European qualifying for the 2018 World Cup in Russia.
The Group I match between Croatia and Kosovo was abandoned due to heavy rain and postponed until Sunday.
With Isco leading the way, Spain dominated from the start and comfortably defeated Italy 3-0 in the group's standout match at the Santiago Bernabeu Stadium.
Italy hadn't lost a World Cup or European Championship qualifier since 2006. Spain's last loss in World Cup qualifying was in 1993.
Isco got the better of Italy goalkeeper Gianluigi Buffon from a free kick early in the game, then outsmarted the Italian defense with a low shot just before halftime. Substitute Alvaro Morata scored the third goal in the second half.
The result left Spain with 19 points, three more than Italy and seven more than third-place Albania, which needed two second-half goals to beat last-place Liechtenstein 2-0 at home.
Israel missed a chance to move within four points of Italy after a 1-0 home loss to Macedonia.
Both Italy and Spain had won all their group matches apart from a 1-1 draw against each other in Turin.
Liechtenstein has lost all of its seven matches, being outscored 26-1.
After drawing five of its six qualifiers, Wales defeated Austria 1-0 as Bale returned from suspension and produced some magic, including a scissors kick in injury time.
But it was substitute Woodburn who rescued his country shortly after coming off the bench. He collected the ball after the Austrian defense failed to clear a cross in the 74th and hit an unstoppable right-foot drive from 25 meters (yards) away.
Serbia relied on Mijat Gacinovic and Aleksandar Kolarov to beat Moldova and take control of the group with 15 points. Ireland is two points behind after being held to a 1-1 draw at Georgia. The two nations play each other in Dublin on Tuesday in a potentially decisive matchup.
Wales moved to 11 points and remains in contention.
Georgia has four points and Moldova is last with two points.
Andriy Yarmolenko celebrated his 70th international appearance with two first-half goals to give Ukraine victory over Turkey.
The result moved Ukraine top of the group after Iceland lost 1-0 at Finland.
Finland had earned just a single point from the previous six qualifiers - a draw against Kosovo.
Ukraine has 14 points while Croatia and Iceland are one point behind. Turkey is three points back on 11.
The game between Croatia and Kosovo was suspended midway through the first half due to adverse weather conditions, and later abandoned.