Ms O'Brien's appointment comes after a lengthy national search for an educator to lead GSSC when its campus formally opens at the beginning of next year.
Department of Education and Training's north-east Victoria regional director Terry Bennett said Ms O'Brien was a "standout" candidate.
“Barbara has already shown she has the skills, experience and vision to make GSSC all it can be,” he said.
“To have those qualities in a candidate with such a proven career and personal commitment to families in Greater Shepparton is a bonus.”
For more than three decades Ms O'Brien has worked with teachers and students across Greater Shepparton.
Apart from an initial year of teaching in Melbourne, Ms O'Brien has worked locally — first as a classroom teacher at Mooroopna, Tallygaroopna and Gowrie St primary schools.
She then went on to become leading teacher, assistant principal and principal at Wilmot Road Primary School before heading Grahamvale Primary School.
Working at multiple schools as a network leader, Ms O'Brien moved to higher education as principal of Benalla P-12 College, where she oversaw the merger of secondary schools.
She has been working with GSSC as its senior education improvement leader since 2020.
“I am thrilled to be taking on the leadership of GSSC at such a historic and exciting time for our secondary students,” Ms O’Brien said.
“With the Shepparton Education Plan and the development of amazing new college facilities at Hawdon St, we have never had such investment in improving the educational outcomes of our young people.
“A good education is so important in allowing our students to pursue their dreams and aspirations in life; I feel privileged to lead GSSC at a time when we are offering them unprecedented opportunities and pathways to do so.”
Ms O'Brien said her focus as executive principal would be building a "strong, inclusive and caring" culture at the school.
Ms O'Brien has formally taken on the position from the end of term two.
Construction of Greater Shepparton Secondary College is entering its final stages, with the new college on track to open for the 2022 school year.