Limited by foul trouble the past two games, the 6-foot-11 Towns was forceful all night in helping the unbeaten Wildcats (35-0) cruise to the site's most lopsided outcome of the day after three 1-point finishes at the KFC Yum! Center.
Saskatoon's Trey Lyles added 10 points and six rebounds, Tyler Ulis scored 11 and Willie Cauley-Stein grabbed 11 rebounds for the Wildcats, who face Cincinnati on Saturday.
Hampton's Quinton Chievous shook off an ankle injury sustained in Tuesday's First Four upset of Manhattan to score 22 points with 10 rebounds, but the Pirates (17-18) were no match for Kentucky after the first 10 minutes and trailed by as many as 35 midway through the second half.
Hampton shot just 29 per cent from the field.
Though Kentucky had just three days of rest before beginning the final phase of its quest to become the program's first unbeaten national champions, the Wildcats benefited from having to travel just 85 miles west for their tournament opener. The home court of in-state archrival Louisville has served them well in the tournament, providing the launching point for their last NCAA title in 2012.
Kentucky had an arena full of blue-clad fans loudly cheering for more good fortune. Big Blue Nation was also patient, waiting through an overtime warmup between Cincinnati and Purdue before the game finally started at 10:19 p.m. ET.
The late, late tipoff might explain why the Wildcats were a step slow getting started against the Pirates, who faced long odds against Kentucky despite surpassing expectations with Tuesday night's wire-to-wire win over Manhattan in the First Four game at Dayton.
Hampton made things intriguing for a few minutes with a 4-3 lead and a later a 9-all tie that pleased its contingent of fans. Kentucky took charge from there, gaining its first double-digit lead with about six minutes left in the first half and didn't look back.
A 21-8 run over the final 7 1/2 minutes provided a 41-22 halftime lead for Kentucky. Towns exploited the smaller Pirates for several power moves. He finished 8 of 12 from the field and 5 of 6 from the line after combining for 16 points and 10 rebounds the past two games.
A 9-0 spurt over 2:25 of the second half put it firmly out of control against Hampton and gave Kentucky the strong tournament start it sought, albeit slowly.
LOSS OF A FRIEND
Columnist Ira Combs, 61 and a fixture at Wildcats games, died earlier Thursday after collapsing while picking up NCAA Tournament credentials. Coach John Calipari, Kentucky athletic director Mitch Barnhart and NCAA president Mark Emmert expressed sympathies for a founder of the Joe B. Hall Prep Classic named for the former Wildcats coach.
Hampton: Deron Powers recorded both of the Pirates' assists, one in each half.
Kentucky: The Wildcats shot 46 per cent, outrebounded Hampton 51-31 and controlled the paint 44-20. ... Towns and Cauley-Stein combined for all five Kentucky blocks.
HAMPTON: Season ends.
KENTUCKY: Faces Cincinnati on Saturday.