Kunc also contributed eight rebounds and three assists for the Cyclones (7-1). Robert Jones had 11 points, four rebounds and three assists.
Posh Alexander led St. John's (8-1) with 14 points.
Iowa State turned the tables on the full-court pressing Red Storm, forcing 20 turnovers and holding St. John's to 36% shooting.
''We work every single day on our defensive pressure,'' Holmes said. ''We want to turn teams over. We want to be the best defensive team in the country.''
The Cyclones opened the game with a 17-2 run, capped off by a Gabe Kalscheur 3-pointer at the 10:47 mark of the first half.
In the opening 9 minutes, St. John's went 0 for 8 shooting and committed nine turnovers. Rafael Pinzon hit a 3-pointer for the Red Storm's first basket, with 9:54 left in the half.
''It's a lesson learned,'' St. John's coach Mike Anderson said. ''One of the things you've got to do when you go on the road is, you've got to be able to shoot the basketball. That cures a lot of ills.''
The Cyclones led 33-22 at the break. St. John's went 6 for 23 shooting (26.1%) in the first 20 minutes.
A 3-pointer from Holmes gave Iowa State a 44-29 margin early in the second half. Osun Osunniyi's dunk made it 47-30 with 13 minutes remaining.
''Our guards did a great job cutting,'' Iowa State coach T.J. Otzelberger said. ''With St. John's, they pressure you and want to spread the floor a little more. So, you can get some more of those cuts to score, some more of those opportunities.''
The game was part of the Big12/Big East Battle.
Iowa State will likely remain in the top 25 after making its season debut this week. St. John's was playing its first game outside of New York City and began this weekend as one of just 15 unbeaten teams nationally.
St. John's opens Big East play Wednesday with a home game against DePaul.
Iowa State travels to rival Iowa for a Thursday showdown that will air of FS1.
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