Pell, who serves as Pope Francis' chief financial adviser, pleaded not guilty before an Australian magistrate. He was ordered to appear in court again on Wednesday.
The charges against Pell were first announced last June.
Melbourne Magistrate Belinda Wallington previously agreed to discharge some of the most serious charges against Pell, the highest-ranked Catholic in Australia, but she said the case against Pell was strong enough to warrant a trial by jury.
Over the last four weeks, the court heard allegations of sexual offenses that allegedly took place at a swimming pool, cinema and a cathedral between the 1970s and 1990s, according to Australia's 9News.
Police in the Australian state of Victoria have charged Pell, 76, with multiple counts of sexual assault, but details about the charges have not been disclosed. Pell vowed to "defend" himself against the allegations in a statement released on his behalf early Tuesday.
“Cardinal George Pell has at all times fully cooperated with Victoria Police and always and steadfastly maintained his innocence. He has voluntarily returned to Australia to meet these accusations,” the statement said. “He will defend the remaining charges.”
Pell thanked those who have supported him “during this exacting time” and said he was “grateful for their continuing support and prayers,” according to the statement.
Pell has not been asked to resign by Francis, who has vowed zero tolerance for sexual-related offenses. The pontiff granted Pell a leave of absence last year "so he can defend himself."
"The Holy See has taken note of the decision issued by judicial authorities in Australia regarding His Eminence Cardinal George Pell," Greg Burke, director of the Holy See Press Office said in a statement Tuesday. "Last year, the Holy Father granted Cardinal Pell a leave of absence so he could defend himself from the accusations. The leave of absence is still in place."
The Vatican issued a similar statement last year when the charges against Pell were initially announced.
"The Holy See has learned with regret the news of charges filed in Australia against Card. George Pell for decades-old actions that have been attributed to him," the Vatican said in a statement last June. "The Holy Father, having been informed by Card. Pell, has granted the cardinal a leave of absence so he can defend himself."
In 2014, Francis appointed Pell the Vatican prefect of the secretariat for the economy. Pell, who was ordained as a priest more than 50 years ago, is the highest-ranking Vatican official to face charges in the Catholic Church's multiyear sex abuse scandal.
Pell voluntarily spoke with Australian police officials in Rome in 2016 about alleged sexual assaults in Ballarat, Australia, from 1976 to 1980 and in East Melbourne from 1996 to 2001.
The Vatican said Pell has "openly and repeatedly" condemned abuse against minors and noted his support for the Pontifical Commission for the Protection of Minors.
ABC News' Phoebe Natanson contributed to this report.