The Premier League side's two previous ventures into Europe's elite club competition saw them crash out in the group stages, finishing third in 2011-12 and bottom last season.
Manuel Pellegrini takes charge of his first Champions League match since replacing Roberto Mancini at the helm at the Etihad Stadium.
His side have hardly enjoyed ideal preparation for their first foray into Europe this season, however, after being held to a 0-0 draw by Stoke City on Saturday.
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|16/1||Man City are 16/1 with BetVictor to beat Viktoria Plzen 3-0
For their part, Plzen head into the competition in superb form, having won all six of their qualifying matches.
They also top their domestic league table after an unbeaten start consisting of six victories and two draws.
The hosts - who will likely look to their top scorer in qualifying, Marian Cisovsky, to provide their goal threat - will undoubtedly start as underdogs.
With City picking up just the one away win in six in the Champions League to date, coupled with the fact that Plzen have only failed to triumph in one of their previous 11 home matches in Europe, they will retain some hope of an upset.