Kansas made just 2 of 21 three-pointers (9.5 percent), falling 71-61 to 11th-seeded VCU on Sunday afternoon at the Alamodome in San Antonio, Texas.
VCU, meanwhile, made 12 of its 25 threes (48 percent).
"It's a disappointing day, obviously. We're crushed," KU coach Bill Self said. "But also, I think at the end of the day, we tried real hard and just came up empty against a team that was better than us today."
Marcus Morris led KU with 20 points on 8-for-19 shooting with 16 rebounds. Tyshawn Taylor added 14 points, while Markieff Morris had 13 points and 12 rebounds.
KU fell behind 39-21 in the first half before closing to within two with 13:13 left in the game. The Jayhawks didn't get any closer.
"Probably one of the poorest shooting nights we've had as a team," KU guard Tyrel Reed said. "But credit to VCU. Our shots weren't falling."
The Jayhawks made just 22 of 62 shots for 35.5 percent, their lowest field-goal percentage in the last two seasons. The team's 9.5 percent three-point shooting also was its worst outing in the last two years.
KU ends its season with a 35-3 record.