"I resigned from my post as a trade minister effective on February 1st," he told reporters, adding that President Susilo Bambang Yudhoyono had accepted his decision.
The minister announced his intention in September to stand down and contest the ruling Democratic Party's convention to decide its presidential candidate.
Wirjawan added he would "devote all my time and energy for the success of this noble task."
The winner will represent the party in the July vote, but the nominee will face a tough challenge to stay in power after two terms under Yudhoyono due to its declining popularity amid graft cases implicating high-rank officials.
Yudhoyono cannot run a third time, according to the country's constitution.
Several recent polls showed that Wirjawan has a slim chance of winning the presidential election due to the popularity of the current Jakarta governor Joko Widodo. Widodo has yet to announce any plan to run.
It remains unclear who will replace Wirjawan as trade minister. The resignation of the respected former investment banker may add to business and investment uncertainties in Southeast Asia's biggest economy, which has struggled to cope with its prolonged current deficit and weakening currency.