The Tigers (7-5, 5-4 Big 12) head to the SEC next season, and Kansas has said it has no intention of playing Missouri out of conference.
Missouri improved its bowl prospects by winning its third straight game to finish the regular season, doing so with coach Gary Pinkel back on the sideline. He was suspended for last week's come-from-behind win over Texas Tech following a drunken-driving arrest.
On the other sideline was Turner Gill, who may have coached his final game for Kansas (2-10, 0-9).
Gill is just 5-19 in two seasons in charge, and 10 straight losses to finish this season - many in lopsided fashion - may have sealed his fate. Kansas athletic director Sheahon Zenger has said he will decide soon about Gill, who has three years and $6 million left on his contract.
There was a meager crowd of 47,059 on hand at Arrowhead Stadium to see what could be the finale of a series that began in 1891, and is second in games played only to Wisconsin-Minnesota among major college football rivalries.
Jordan Webb finished with 60 yards passing and two interceptions for the Jayhawks (2-10), who managed only 137 yards of total offense. James Sims carried 15 times for 35 yards.
Franklin was the Jayhawks' best player in the first half. The Missouri quarterback, who had gone four games without throwing an interception, was picked off by Tyler Patmon midway through the first quarter - the first of three consecutive drives by the Tigers that ended in an interception.
On their ensuing series, Franklin was pressured by Toben Opurum and threw a wobbly pass that was intercepted by Greg Brown near the Missouri sideline. He returned it 20 yards to the Tigers 15, but the Jayhawks could manage only a field goal when three plays netted them minus-1 yard.
Franklin's third pick was the most costly.
Facing third-and-16 from the 47, the sophomore quarterback threw a pass that was undercut by Kansas safety Bradley McDougald. He started up the Missouri sideline, bobbing and weaving his way through traffic before sprinting the rest of the way for a 57-yard touchdown return.
The first pick-six for the Jayhawks since Sept. 19, 2009, made it 10-0.
The Tigers finally got something going on offense later in the second quarter, marching 59 yards in 5:12 - largely on the ground - before Trey Barrow kicked a 23-yard field goal.
The Jayhawks looked like a two-win team on their first possession of the second half, when three plays netted minus-2 yards. When they tried to punt it away, the snap nearly went over the head of Ron Doherty, giving Missouri the ball at the Kansas 14-yard line. It took Kendial Lawrence only three carries to tie the game at 10.
After the Jayhawks were forced to punt, the Tigers went 93 yards for a touchdown, the big plays a 22-yard completion to Jerrell Jackson, a 20-yard run by T.J. Moe and a 25-yard TD pass from Franklin to Wes Kemp in the back of the end zone. The pass was initially called incomplete, but the officials reviewed it and ruled that Kemp's feet came down inbounds.
Franklin hit Marcus Lucas for a 53-yard touchdown on the first play of the fourth quarter.