Kelenna Azubuike added 16 points for Kentucky (14-2, 5-0 Southeastern Conference), which made a season-high 11 3-pointers in 20 attempts to win for the 14th time in its last 15 meetings with LSU (9-6, 2-2).
The Wildcats have won four straight since losing to No. 2 Kansas on Jan. 9.
LSU, which had a three-game winning streak snapped, lost for the 38th time in 42 games against the Wildcats in Lexington. The Tigers' last win at Kentucky came in 1989.
The loss was LSU's worst since falling by 32 points to Florida in January 2002.
Kentucky shot 54.2 percent from the field, the third time in four games the Wildcats - who rank 10th in the SEC in that category - have exceeded 50 percent.
Defensively, the Wildcats' trio of Chuck Hayes, Randolph Morris and Shagari Alleyne limited LSU's inside duo of Brandon Bass and Glen Davis. Bass scored 14 points, three under his average, while Davis went 1-of-5 from the field and scored nine points, five under his average.
Bass had 10 rebounds and Davis had 12 rebounds, helping LSU to a 37-32 edge on the boards. But that wasn't enough to offset the Tigers' 33.3-percent shooting effort or 18 turnovers. LSU went 5-of-22 (22.7 percent) from 3-point range.
The Wildcats, coming off a season-low 53-point outing against Mississippi in their previous game, posted their highest-scoring first half of the season and led 49-36.
After falling behind 5-0, Kentucky scored 23 of the next 26 points to take a 23-8 lead. Kentucky led by as many as 20 in the first half before LSU closed on a 9-2 run.
LSU pulled within eight points with 13:43 left, but Kentucky freshman Joe Crawford - in his first game since leaving, then returning a week later to the Wildcats - made two free throws and followed with a 3-pointer, building Kentucky's lead to 62-49.
Kentucky's superior depth wore down the Tigers in the final minutes. Twice in two minutes, 6-foot-1 freshman point guard Rajon Rondo drove for easy layups over LSU's 6-foot-8 Bass, and in between, assisted on baskets by Sparks and Hayes.
Kentucky led by as many as 33 points.
Hayes and freshman Ramel Bradley added 10 points each for Kentucky, while Alleyne had nine points, six rebounds and four blocked shots.
Antonio Hudson scored 11 points for LSU.