In the preface, Smollett acknowledges the connections of his novel to the two satirical picaresque works he translated into English: Miguel de Cervantes' Don Quixote (1605–15) and Alain-René Lesage's Gil Blas (1715–47) The novel is set in the 1730s and 1740s and tells the life story (in the first person) of Roderick "Rory" Random, who was born to a Scottish gentleman and a lower-class woman and is thus shunned by his father's family.

Random's paternal grandfather coerces a local school master into providing free education for the boy, who becomes popular with his classmates (some of whom he encounters again in subsequent adventures) and learns Latin, French, Italian and ancient Greek.

Roderick spends much of the novel trying to attract the attention of various wealthy women he meets, so that he can live comfortably and take up his rightful entitlement as a gentleman.

[1] Smollett offers a vicious portrayal of hypocrisy, greed, deceit and the snobbery peculiar to the times, especially among the upper and middle classes.

He exposes the brutality, incompetence and injustice of the Royal Navy at the Battle of Cartagena in 1741 and in relation to preferment, promotion and medical treatment.

The novel embraces common 18th century topics such as privateering, slavery, prostitution, dowries, homosexuality, debtor's prison (the Marshalsea), political and arts patronage, the clergy, the practice of medicine, and corruption.