Cal Poly had beaten a Pac-12 team the last two seasons: Southern California two years ago, then-No. 11 UCLA last season.
No. 6 Arizona, though, proved to be a little too much for the Mustangs.
Still, they kept it close before falling 73-62 on Friday night in front of a raucous McKale Center crowd in a game that Cal Poly sharpshooter Kyle Odister says will only help down the road.
"This is the atmosphere that you want to be in," he said. "You want to go to the NCAA tournament, so this will prepare us for the whole season."
Odister, the hero of the win over UCLA, scored 21 points on 7-of-14 shooting from 3-point range.
"We knew we were outsized coming into the game," he said, "so we knew we were going to have to hit shots from the outside to stay in the game. We did that in the first half."
Cal Poly trailed only 37-34 at halftime.
But the deep, talented Wildcats wore down the Mustangs after that.
Aaron Gordon had 13 points, 10 rebounds and four blocked shots in his debut for Arizona, leading six Wildcats in double figures.
Arizona took the lead for good with just under 11 minutes left in the first half but the Mustangs stayed close until the final minutes.
Wildcats coach Sean Miller wasn't surprised that his team struggled against what he considered a good early season opponent.
"Our upside is, I think, significant but we just have so many players in new roles that you can't expect us to be a great team right now," he said. "We're far from it. ... I do think that down the road we're going to be a much better team than you saw tonight."
Gabe York scored 12 points, Brandon Ashley, Kaleb Tarczewski and Nick Johnson had 11 apiece and Rondae Hollis-Jefferson added 10 for the Wildcats, who were 20 of 36 from the free throw line.
Chris Eversley added 17 points for the Mustangs, who were 11 of 26 on 3-pointers.
Gordon had been limited in practice over the past 10 days or so because of a groin strain.
"In tonight's game, in the 33 minutes that he played, 20 of the 33 you could kind of really see him at full speed," Miller said. "And he did the best he could for about 10 to 13, especially in the second half. You could see he wore down a little bit. ... But he did a lot of things tonight. He makes his free throws and he has not a good night, but a great night."
Gordon was 2 of 6 from the free throw line.
"I missed too many free throws but I was a little nervous at first," he said. "I finally told myself that basketball is basketball no matter what level or where you play at, it's always the same game."
Arizona didn't get the lead to double digits until Gordon blocked a shot, then converted a three-point play at the other end to put the Wildcats ahead 56-45 with 9:47 to play. Cal Poly never got closer than seven points after that.
"For us to come into a top-five atmosphere, we have to play A-plus," Cal Poly coach Joe Callero said. "We played a solid first half, but it's a 40-minute game and it doesn't matter how close you are at halftime. Their execution and athleticism wore us down."
A 9-0 run on three straight 3-pointers, two by Odister and one by Michael Bolden, put Cal Poly up 19-17 with 12 1-2 minutes left in the half.
C.J. McConnell, the point guard transfer from Duquesne, hit a 3 from the corner to put Arizona back on top 20-19 and the Wildcats led the rest of the way.
Dave Nwaba scored all 12 of his points in the first half for the Mustangs.
York's 3-pointer started a 7-0 spurt that put Arizona up 44-36 barely 4 minutes into the second half. Eversley's 3-pointer cut it to 51-45 with 11:54 to play, then Johnson made a 10-footer and Gordon, after blocking a shot, came down the court, scored and was fouled for the three-point play that made it 56-45.
The Wildcats led by as many as 15 points down the stretch.
Arizona was the highest-ranked team the Mustangs ever have played.