Couillard strolled to victory in the Montreal riding of Outremont with more than 50 per cent of the vote.
The win was hardly surprising because the riding has traditionally been Liberal and because the governing Parti Quebecois and the Coalition for Quebec's Future did not field candidates.
Couillard has been Liberal leader since last March.
Outremont became available after former Liberal finance minister Raymond Bachand resigned following a failed leadership bid. Bachand won with 41.5 per cent of the vote last year.
The Liberals also emerged victorious in a second byelection in Montreal on Monday, as David Heurtel romped in Viau with about 60 per cent of the vote.
The Liberal wins give Couillard's party 50 members in the 125-seat national assembly, four behind the PQ. The Coalition has 18, while the leftist Quebec solidaire has two. There is one Independent.
Viau became vacant when Liberal incumbent Emmanuel Dubourg resigned to run successfully for the federal Liberals to replace former MP Denis Coderre.
Dubourg won in 2012 with 47.3 per cent support.
Couillard thanked his supporters at an election-night rally and said he had been baptized in the church where he was speaking.
"This shows one thing — that all dreams are possible in Quebec," Couillard said. "It takes certain ingredients. It takes courage. It takes hard work and it takes luck."
Couillard is expected to be sworn in next week, while the national assembly resumes sitting on Feb. 11 after its winter break.
A general election is widely expected in the spring.