Music videos played on the channel primarily consist of indie rock, pop punk and hip-hop along with limited original programming.

According to its promotional materials from 2004 to 2018, MTVU broadcast exclusive content dedicated to aspects of college life, including music, news, and on-campus events.

Currently, MTVU plays a mix of music videos with an emphasis on emerging artists and short interestistial segments focusing on college life.

The Freshmen featured three rotating student panelists discussing new music videos and was hosted by Kim Stolz; Stand-In brought celebrities and intellectuals into college classrooms to teach for a day, and featured people such as Nobel Laureates Elie Wiesel and Shimon Peres; Madonna; John McCain; Marilyn Manson; and Jhumpa Lahiri.

MTVU formerly broadcast its own semi-annual awards show, the MTV Woodies, which it states recognizes "the music voted best by college students."

Winners at the 2009 Woodie Awards included Green Day, Kings of Leon, Matt & Kim, NeverShoutNever, Tech N9ne and Hotel of the Laughing Tree.

Its Half of Us initiative won a Peabody Award in 2007 "for its extensive research and dedication to fighting depression and creating quick routes to convenient solutions.

MTVU formerly co-sponsored the ecomagination Challenge with GE, which aimed to empower college students to solve environmental problems on campuses.