Captain Ronaldo, making his 160nd international appearance, scored four as Portugal won 5-1 in Vilnius and strengthened their position in Group B after a sluggish start.
For Ronaldo it was a second hat-trick in three internationals. The victory over Lithuania, 130th in the world rankings, kept brought Portugal five points behind Ukraine at the top of Group B, with a game in hand.
Vytautas Andriuskevicius scored the hosts' only goal before William Carvalho added a fifth for the reigning champions at the end.
Serbia beat Luxembourg 3-1, as Aleksandar Mitrovic netted twice, to solidify their grasp on third place. They are a point behind Portugal.
In Southampton, Gareth Southgate's England side trailed early on to Kosovo, ranked 120th in the world, when Valon Berisha scored after 34 seconds. England replied with a first-half goal binge that ended with Jadon Sancho scoring twice to make it 5-1 at the break.
The visitors claimed two back in the second half, including a second for Lazio midfielder Berisha, but the 5-3 victory put England three points clear in Group A, ahead of the second-placed Czech Republic, who beat Montenegro 3-0.
In Paris, the world champions made light work of beating 136-ranked Andorra 3-0. It was Les Bleus' 100th match at the Stade de France.
Kinglsey Coman, Clement Lenglet, with his first on the international goal, and Wissam Ben Yedder clinched three points to keep France locked with Turkey at the summit of Group H.
The Turks beat Moldova with ease in a 4-0 victory in Chisinau. But Iceland, who had been level with the top two suffered a blow as they lost 4-2 in Albania to drop three points behind the top two.