Measuring by majors at graduation, that would be biology in the College of Letters & Science (L&S). In the 2016–17 academic year, 563 undergrads graduated with a degree in biology, beating out economics (547), psychology (346), political science (332), and communication arts (291). From 2014 to 2016, econ (also an L&S major) had been the most popular major. Those five majors have been the most popular for the past five years (except in 2012–13, when history briefly knocked comm arts out of the number-five slot). Among master’s students, social work has been the number one major at graduation for the past five years, followed by accounting, computer sciences, electrical engineering, and MBA/general management. For doctoral students, chemistry is number one, followed by computer sciences, curriculum and instruction in the School of Education, electrical engineering, and economics.
If we're talking about popularity based on current enrollment in classes, the most popular (with the exception of "no major," which currently accounts for more than 8,000 students) would be computer sciences. In the Spring 2018 semester, there were 1,576 students with a declared computer-sciences major to biology's 1,281; econ's 1,158; and psychology's 1,149.