Injustice in Tsarist Russia
This might go without saying, but one of the main features of the novel is that it criticizes Russian government, especially the Tsarist Russia of yesteryear, but even the author's own experience of Russia seems to be on display. Remember that the novel was published in the 1960's, at the height of the Soviet Union and the Cold War.
Messianic justice
The most pronounced theme is the astonishing similarity of Yakov and Jesus Christ. The book even focuses its main plot structure around the death of a Christian. Yakov is accused of anti-Christian sentiments which is supremely ironic, since his own imprisonment is obviously Christian in tone, or at least Messianic.
For instance, Yakov and Jesus are both Jewish. They're both carpenters. Their stories center around an unfaithful wife (Israelites and Christians both use marital unfaithfulness as a central image for understanding man's relationship to God, and Yakov's wife was also unfaithful, and in both accounts the unfaithful wives are loved, forgiven, and accepted). They are both the victims of an unfair, totalitarian regime, and both the Roman government and the Tsarist government actively oppressed the Jews. Both are imprisoned although they are innocent, and in both cases, their relationship to injustice seems to represent their role as a suffering servant for the masses.
The unique plight of Jewish people
Yakov correctly notes during his outburst that his being Jewish was a main cause for bad things happening to him. When the government needed to accuse a random person, they automatically chose to select a Jew. This unfairness is historically common, since the Jews have been an oppressed people group in almost every nation at some time or another. Antisemitism in the early 20th century was rampant in most of Europe. Yakov talks about these things after being freed.