The Bulldogs pushed right back.
Shelvin Mack scored 23 points and Gordon Hayward produced his fourth straight double-double, leading No. 18 Butler to its 17th consecutive victory, 70-53.
"Our mentality in the second half was getting to the basket," said Hayward, who finished with 15 points and 12 rebounds. "If you can go inside-out, it's always good."
Butler (25-4) has never played better as the Saints found out in this year's BracketBusters' feature matchup.
Both teams had already clinched regular-season conference championships and came into Saturday's game as two of college basketball's hottest teams. Butler and Murray State, a 75-66 winner over Morgan State on Saturday, have both won 17 straight -- the longest streak in the nation.
That's a school record for Butler, which can wrap up the first perfect Horizon League season since 1995-96 with a win at Valparaiso on Friday.
Last week, Siena (22-6) had the nation's longest winning streak, 15 games, until losing at Niagara. Still, the Saints had won 16 of 17 coming into Saturday.
But against Butler, they got outpunched.
Siena shot 33.9 percent from the field, made only two 3-pointers and fell more than 23 points short of its season scoring average.
Clarence Jackson, with 24 points, and Ryan Rossiter, with 10 points and nine rebounds, were the only Siena players to reach double figures. And after Siena outscored Butler 20-12 in the paint in the first half, the Bulldogs had an 18-14 advantage there over the final 20 minutes.
The combination kept the Saints winless on the road against ranked opponents since they made the jump to Division I in 1976-77.
"We have to play with a greater level of intelligence," Saints coach Fran McCaffery said. "It was still a one-possession game with 10 minutes to go. We'll try to be better at that part of the game in the future."
That's the best Siena can hope for now after falling to a team that wasn't even full strength.
Butler forward Willie Veasley missed the game with a sprained left knee after starting every other game this season. Coach Brad Stevens said the senior worked out before the game but was held out because he was not quite 100 percent.
His teammates made up for it.
The Bulldogs shredded Siena's zone early, making four 3-pointers -- two by Avery Jukes, Veasley's replacement -- in the first 3½ minutes. That helped Butler jump to a 16-7 lead.
So McCaffrey's team got physical.
On defense, the Saints repeatedly clogged the middle and prevented Butler's players from getting to their spots.
On offense, the Saints routinely drove into the middle, lowered their shoulders and drew contact.
The strategy threw off Butler, which scored only 12 points over the final 15:55 of the half and trailed 31-28.
So the Bulldogs changed tactics.
"I think one of the keys was that we had to get used to the way the game was being played," Stevens said. "That's one thing about [us] playing those games earlier in the year. They've played a lot of games like this, they've played a lot of minutes, so they know what to expect, they know how to handle it."
Even if that meant dealing with yet another curveball.
Just as the Bulldogs appeared ready to take control early in the second half, reigning Horizon League Player of the Year Matt Howard was called for his fourth foul with 16:29 to go.
Hayward and Mack started driving hard to the basket, igniting a 9-2 run that gave Butler a 41-36 lead 14:43 to go. And with the inside game working, the perimeter was suddenly open again for Butler's long-range shooters. Zach Hahn responded with consecutive 3s that gave Butler a 47-38 lead with 10:56 to go.
Siena never got closer than seven points the rest of the way as Veasley, Jukes and Nick Rodgers -- the three seniors -- celebrated after closing out a 13-0 home season.
The victory was Stevens' 81st in three seasons at Butler, matching the NCAA record. Mark Fox, who coached at Nevada until leaving for Georgia this season, and Gonzaga's Mark Few both won 81 games in their first three seasons as a head coach.
And it was the sixth straight double-digit win for the Bulldogs.
"Their strength is scoring in the paint, all of those things," Stevens said. "Our guys did a really good job of staying balanced, certainly the paint was an emphasis to us."