An opening day victory for the visitors has put them in good stead in the section.
Match preview
It was the Sparta Prague show for the Czech Republic in their 3-1 win over Poland on Friday night.
Despite playing in the stadium of their rivals Slavia Prague, Sparta's deadly duo Tomas Cvancara and Jan Kuchta were among the goals, as was the club captain Ladislav Krejci.
It was the perfect start for manager Jaroslav Silhavy, who entered the qualification campaign under some pressure following a poor UEFA Nations League showing and failure to reach the 2022 World Cup.
Four straight defeats to finish their Nations League section, scoring only once, and losing to Sweden in a World Cup playoff left his job in jeopardy.
However, Friday's win leaves them big favourites now to progress, with the top two guaranteed a spot at the finals.
The 3-1 scoreline also means that 10 of their last 12 victories have seen the Czechs win by two or more goals.
Despite being huge underdogs for this encounter, Moldova come into the tie four games unbeaten in competitive fixtures.
A more accurate statistic for them to prepare for this game though, is that they are on a 20-game losing streak against nations ranked in the world's top 100.
That shows the benefits of the Nations League for a country like Moldova, but they were still surprisingly beaten to promotion by Latvia in League D, even though they amassed 13 points from six games.
Since then, home friendly defeats to Azerbaijan and Romania may have knocked confidence slightly, but they managed to avoid defeat in their opening qualifier.
Ion Nicolaescu's late penalty salvaged a point for Moldova against the Faroe Islands, but in what was the easiest game on paper in the group, Serghei Clescenco's side would have preferred a win on home soil.
They will be looking to avoid finishing bottom of their section again after doing so in qualification for both Euro 2016 and Euro 2020.
Moldova's 2022 World Cup qualifying campaign started also with a 1-1 draw against the Faroe Islands, but they went on to lose all nine remaining matches in the group, so avoiding a similar scenario will be the aim, especially considering they lost their second fixture 8-0 that time around.
Moldova Euro Champ Qualifying form:
D
Moldova form (all competitions):
W
W
W
L
L
D
Czech Republic Euro Champ Qualifying form:
W
Czech Republic form (all competitions):
L
L
L
W
L
W
Team News
Patrik Schick was unavailable for the Czech side on Friday, but the Bayer Leverkusen man may struggle to dislodge the attacking trio of Kuchta, Cvancara and Adam Hlozek, after their performances against Poland.
Given the shortcomings of their upcoming opponents though, Silhavy may opt to go with an extra attacking option from the start here.
Should Schick miss out once more, Fiorentina's Antonin Barak and the in-form Vaclav Cerny will hope for some game time.
Moldova's saviour on Friday, Nicolaescu, has 17 goals in 24 domestic outings for Beitar Jerusalem in Israel this season, so will act as the side's main threat.
Oleg Reabciuk of Olympiacos and Artur Ionita, who has spent nine years in Italy, represent the other standout members of the squad.
The experienced Igor Armas could come into the side after missing the draw against the Faroes, joining his two Voluntari teammates Vadim Rata and Vitalie Damascan who started.
Clescenco started with a 5-4-1 formation in that game and could be even more cautious here given the step-up in opposition, so Virgiliu Postolachi could be sacrificed for a more defensive option.
Moldova possible starting lineup:
Railean; Revenco, Craciun, Mudrac, Armas, Posmac; Platica, Rata, Caimacov, Damascan; Nicolaescu
Czech Republic possible starting lineup:
Pavlenka; Holes, Brabec, Krejci; Coufal, Kral, Soucek, Cerny; Cvancara, Hlozek, Kuchta
We say: Moldova 0-4 Czech Republic
The Czechs showed a ruthless edge in beating Poland on Friday and they should be able to fill their boots against the weakest side in the section.