Spain secured its 11th straight World Cup appearance aided by Italy's home draw against Macedonia on Friday, while Serbia blew a chance to make it to next year's finals in Russia after a loss at Austria.
Spain comfortably defeated Albania 3-0 in a match in which defender Gerard Pique, an outspoken defender of Catalonia who had been harassed by Spanish fans during the week, received a mixed reaction from the home supporters.
"Despite everything that happened this week we were able to play a great match," Isco said. "We have to be proud of having already qualified for the World Cup with one game yet to be played."
Italy practically secured a playoff spot but it was jeered by fans after drawing with Macedonia 1-1 in Turin. Even a victory would have kept the Italians in a difficult position to surpass Spain for first place in Group G because of its worse goal difference.
Serbia needed a win against Austria to clinch its spot from Group D but it lost 3-2 in Vienna, while Wales kept its chance alive by beating Georgia 1-0 despite Gareth Bale's absence.
Iceland stayed on the path to becoming the smallest nation to qualify for the World Cup after beating Turkey 3-0 in Group I.
The group winners automatically qualify, while the best eight second-place finishers from the nine groups advance to the playoffs.
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Serbia conceded an 89th-minute goal in its loss to already-eliminated Austria, while Wales won at Georgia without injured star Gareth Bale thanks to a goal by Tom Lawrence just after halftime.
The Serbs can still secure first place with a home win against Georgia on Monday. But Wales was only a point behind Serbia, and Ireland was another point back and still alive after defeating Moldova 2-0 in Dublin.
Wales and Ireland meet on Monday to decide their fate.
Spain defeated Albania with first-half goals by Rodrigo, Isco, and Thiago Alcantara in a match marked by mixed reaction toward Pique, who was booed and applauded by different parts of the crowd of nearly 30,000 fans in Alicante.
Many fans have targeted Pique for being openly critical of the Spanish government's handling of the independence referendum organized by Catalonia on Sunday, when authorities and voters confronted each other in violent clashes.
Italy's chance of winning the group ended with a surprise draw in Turin. Defender Giorgio Chiellini put the Italians ahead shortly before halftime but Macedonia substitute Aleksandar Trajkovski equalized near the end.
"The jeers at the end were deserved looking at how we played after the break," Italy coach Gian Piero Ventura said.
Liechtenstein fell at home to Israel 1-0 for its ninth straight loss. Liechtenstein has been outscored 35 to one.
Iceland was at the top of the group after its stunning 3-0 win at Turkey. With Finland surprisingly holding Croatia to 1-1 away, and Ukraine taking three points from Kosovo after a 2-0 away win, the tightest group in European qualifying will have to be decided on Monday in the last round of matches.
Iceland leads with 19 points, and Croatia and Ukraine are two points behind. Turkey is out of contention with 14 as well as Finland with 8.
Iceland is a clear favourite when it hosts last-placed Kosovo in its last qualifier, while Croatia has to travel to Ukraine.