Under the plan, employers would have had to pay workers a minimum 22 Swiss francs (about $25 or 18 euros) an hour.
Supporters said the move was necessary for people to live a decent life.
But critics argued that it would raise production costs and increase unemployment.
The minimum wage proposal was rejected by 76% of voters. Supporters had argued it would “protect equitable pay” but the Swiss Business Federation said it would harm low-paid workers in particular.
The issue was the most prominent of several referendums held on Sunday.
A controversial plan to buy 22 Swedish-made Gripen fighter jets for the Swiss Air Force was narrowly rejected by 53% of voters.
It was the trade union-backed proposal to ensure that an annual salary was not less than $53,600 a year that provoked the most debate.
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