The march, which had started peacefully with thousands of students carrying signs and banners demanding reforms, turned into violent clashes as anti-riot police attacked protesters.
Police used water canons and tear gas to disperse the large crowds of students who responded by throwing rocks and other objects at police.
The marches, attended by students and professors, follow a recent decision by the country’s constitutional court to overturn a law that prohibited for-profit companies from controlling universities.
Profit-making from higher education is illegal in Chile, but critics have long claimed that some companies that operate universities have found ways to exploit loopholes in the law, allowing them to turn a profit without re-investing the money towards reduced tuition or improved education.
The protest was the second under Piñera, a conservative billionaire and ex-president whose first term between 2010 and 2014 was marred by massive student protests seeking an education overhaul.
Earlier this week, Piñera sent a bill to Chile’s congress to increase public financing for technical colleges and promised that access to free higher education was “here to stay,” a move seen as intended to defuse tensions with students, but which lacked further action.
Last year, students protested against the so-called "McDonald's law," introduced by Piñera's government to allegedly boost youth employment by regulating them. However, the opposition claimed that it was creating further precariousness of jobs.
Students have been protesting for years, demanding reforms to the education system that were enacted during the 1973-1990 dictatorship.
Piñera's predecessor, leftist Michelle Bachelet, had promised free university education for the poorest 70 percent of the population in 2016. But students complain they have been sidelined from the process.