With orders to kill every male old enough to carry a gun, his raiders dragged men as old as 90 and boys as young as 14 out of their homes and stood them up and shot them while horrified mothers and wives looked on. They slaughtered, pillaged, looted and burned.
When they finally rode away on that bloody summer day in 1863, some so drunk they hardly could stay in the saddle, perhaps 200 men lay dead. Much of Lawrence was in ashes.
The seeds were sown for generations of hatred and also for, of all things, a college football rivalry like no other. No. 2 Kansas and No. 3 Missouri meet for the 116th time Saturday night in Kansas City, Mo., and never before has so much been at stake.
Tracing its roots all the way back to the pre-Civil War days of the lawless Western frontier, the Kansas-Missouri series bristles with history and passion.
For 116 years an anger has coursed through the Kansas-Missouri rivalry. One Kansas coach used to tell his players that Quantrill graduated from Missouri. It wasn't true, but it would work the Kansas players into a frothing rage.
And now here they are about to collide in the biggest and most important game in their long and colorful history. The winner will go to the Big 12 title game on Dec. 1 with its national championship hopes alive.
This one's not merely for bragging rights. It could be the next-to-last-step in one team's climb to a game its fans would not have dreamed of playing when the season began with both the Jayhawks and Tigers unranked. That Kansas and Missouri should need to beat one another to reach that ultimate goal makes the game even more delicious for everyone involved.
"When I first got here from Connecticut," Kansas athletic director Lew Perkins, a former USC Aiken basketball coach, said, "I figured that Kansas State was this school's No. 1 rival. Then I started going around meeting people and everyone would walk up to me and say the same thing, 'Just beat Missouri. That's all I ask.' "
Only 26 years after the final shot was fired in the Civil War and less than 40 miles away from Lawrence, the Missouri-Kansas series began.
Old soldiers and their children may well have been standing in that crowd when Kansas beat Missouri 22-8 in that historic first game in 1891.
Still fresh in their minds would have been memories of dead bodies and burning homes and bloody border raids by both anti-slavery crusaders riding out of Kansas and pro-slavery zealots operating from Missouri.
Southern sympathizers in Missouri had seen homes burned and men murdered, too. John Brown, the famed abolitionist who was eventually hanged by the federal government, operated for a time out of Kansas.
At issue was whether Kansas would be a free or slave state. Missouri, especially Western Missouri, was virulently pro-slavery.
Lawrence, just inside the Kansas border, had been settled mostly by New Englanders who were equally committed against an institution that everybody today agrees was hideous.
"Slavery is certainly not an issue any more," said Paul Stuewe, a historian who has taught at the University of Kansas. "Nobody argues over slavery today. But that bad blood has carried down."