Playing without coach Bill Self, who is recovering from a minor medical procedure, All-American Jalen Wilson led five Jayhawks players in double figures with 20 points while freshman Gradey Dick posted a double-double, scoring 19 points and grabbing 11 rebounds.
Improving to 28-7 on the season, Kansas won their 16th straight first-round game while running their record to 46-13 as a number one seed in the NCAA Tournament.
For Howard, making their first tournament appearance since 1992, when they also lost to Kansas, Shy Odom was the high man with 15 points. The Bison finish their season at 22-13.
Jayhawks open title defense with solid performance against Bison
Kansas guard Kevin McCullar Jr. made the first basket of the game with a pullup jumper, but Howard responded with a dunk from forward Steve Settle III.
Moments later, a three from All-MEAC First Team selection sophomore guard Elijah Hawkins gave the Bison their first lead of the game at 8-5.
The MEAC champions were keeping up with the defending national champions and Settle nailed a three that drew them to within 15-13 before Kansas extended the lead back to six points with 11:28 left in the first half.
"We did a good job in the first half", Settle said. "But when you play a team like Kansas, they'll capitalize on mistakes. We left a lot of meat on the bone in the first half, gave up a lot of free throws, second-chance points and you can't give that up to a team like that."
Hawkins hit a leaner and Marcus Dockery buried a transition three to put the Bison back in front 20-19 to cap off a 7-0 run.
The game started picking up pace in the last ten minutes, with both teams exchanging leads and turnovers multiple times, but Kansas a 13-3 run by the Jayhawks over the final five minutes created separation and gave them a 50-37 advantage at halftime.
Despite getting outrebounded 23-15 in the opening 20 minutes, Howard stayed in the game thanks to hitting five threes.
The second half began with both teams knocking down baskets, matching each other shot-for-shot, but the Bison continued to struggle on the glass as Kansas repeatedly got on the offensive boards, which led to 12 second-chance points.
The Bison played through Odom in the second half as he scored six of the team's first nine points after intermission.
"We dug ourselves in a hole", he said. "In both halves, we gave up points in transition and second-chance point opportunities."
The turnovers continued to mount for the MEAC champions, which led to 20 points off turnovers for Kansas.
The Jayhawks maintained their lead the rest of the way as they advanced to a second-round matchup with eighth seed Arkansas on Saturday.