Quarterback Mike Hartline completed 16 of 20 passes for 213 yards and tied a career-high with three touchdowns. Derrick Locke ran for 102 yards and a score as Kentucky overpowered the Hilltoppers (0-2) when it mattered.
Bobby Rainey ran for 184 yards and two touchdowns for Western Kentucky but couldn't stop the Hilltoppers from dropping their 22nd straight game, the longest active losing streak in the Football Bowl Subdivision.
Kentucky's point total was its highest in a regulation game since scoring 77 against UTEP in 2002.
Western Kentucky coach Willie Taggart had hoped the Hilltoppers could show the Wildcats that "little brother" is starting to grow up.
Though Western Kentucky played much better than it did in a 41-3 loss at Commonwealth Stadium two years ago, the program, which is in its second season as a full-fledged member of the BCS, couldn't match Kentucky's depth.
And the Hilltoppers certainly couldn't match Cobb. Or catch him, for that matter.
Cobb, a first-team All-Southeastern Conference selection a year ago, showcased his many talents against the Hilltoppers and did it with his typical ease.
He converted a fourth-and-1 on Kentucky's first drive to set up a touchdown, then later put Kentucky up 21-7 with a scintillating punt return. He caught the ball at midfield, shook a couple of defenders then sprinted down the right sideline for the score.
Cobb wasn't done. The former starting quarterback tossed a 15-yard touchdown pass to fullback Moncell Allen out of the "WildCobb" formation and completed his rare triple crown with a ridiculously easy 35-yard touchdown reception from Hartline that put the Wildcats up 49-21 in the third quarter.
Cobb finished with 191 total yards as part of an efficient - if not always spectacular - Wildcat offense. Kentucky racked up 482 yards and did whatever it wanted against an overmatched Hilltoppers defense.
Yet the Wildcats were hardly perfect. Rainey became the first Western Kentucky back in 11 years to top 150 yards in consecutive weeks. He put up 155 yards in a loss to Nebraska in the season-opener and was even better against Kentucky.
He darted down the sideline on the game's third play for a 59-yard score and never really stopped. He later added a 1-yard plunge as the Hilltoppers continued to fight despite a nightmarish stretch in the first half when they allowed the Wildcats to reel off 35 straight points.
Kentucky allowed Western Kentucky to put together a pair of 80-yard scoring drives in the second half, not exactly the kind of performance coach Joker Phillips is looking for with a trip to Gainesville, Fla., looming in two weeks.
Even so, the Wildcats were never in any real danger. Not with Cobb and Locke doing what they do. Taggart said during the week his advice to his players when trying to tackle Kentucky's dynamic duo was simple: "Hold on and wait for help."
It didn't come often enough for the Hilltoppers to end their miserable streak. They'll try to snap it next week at home against Indiana while Kentucky will try to improve to 3-0 for the third time in the last four years against Akron.