With Ashley, Arizona hummed along to the best start in program history, beating the likes of Duke, Michigan, UCLA and San Diego State while winning its first 21 games.
The Wildcats' fortunes took a bad turn Saturday night in Berkeley, when they lost to California 60-58 on Justin Cobbs' last-second shot and lost Ashley to an awkward landing while going up for a rebound in the first half.
Ashley injured his right foot on the play and faces the possibility of surgery.
"It's a huge loss for us not to have Brandon for the rest of the season," Arizona center Kaleb Tarczewski said. "But we still feel that even without him, we still have a great team."
A 6-foot-8 sophomore, Ashley is a difficult matchup for opposing teams on offense, an athletic player who can score in the post, drive to the basket and, after spending countless hours working on his shot during the summer, hit from the 3-point line.
Ashley is third on the team in scoring (11.5 points a game) and rebounding (5.8). He shot 47 percent from the floor, including 36 percent from 3, and often gave opposing teams fits with his ability to keep offensive rebounds alive with his long arms.
Now, Arizona (21-1, 8-1 Pac-12) faces playing the rest of the season without one of its best, most versatile players.
"No one expected us to do as well as we have this year; we kind of just let our play do the talking," point guard T.J. McConnell said. "People can write what they want and say that we're not a national championship team, but we're going to work hard every day and they can't take that away from us."
Ashley also is one of the Wildcats' most versatile defensive players, a long, mobile defender who has the reach to block shots inside and out, and the agility to keep smaller players in front of him.
"Are we going to miss Brandon Ashley? No doubt about it," coach Sean Miller said. "But we still can be an excellent team."
The loss of Ashley will force some shuffling for the Wildcats.
Defensively, Arizona should be OK without him.
Freshman Rondae Hollis-Jefferson, who's expected to slide into Ashley's starting spot, is an active and willing defender. At 6-7, he's just an inch shorter and may be better at defending perimeter players than Ashley, playing that end of the floor more like an upperclassman than a first-year player.
Replacing Ashley's offense may be a little tougher.
Hollis-Jefferson isn't quite as polished as Ashley on offense and doesn't have the same range, hitting 1 of his 6 attempts from 3-point range this season while scoring most of his points on drives and putbacks.
With Hollis-Jefferson in the starting lineup, 3-point specialist Gabe York moves into the sixth man role and the rest of the roster moves up a spot.
Miller has kept a fairly tight rotation this season, so now players who hadn't seen many minutes outside of mop-up duty will be counted on more.
Guard Jordin Mayes was a regular contributor the past two seasons but has seen his minutes decrease this season. Matt Korcheck, who redshirted last season, is an active player with a solid build at 6-10, 230 pounds, though he has played in just 10 games this season.
Freshman Elliot Pitts, who's appeared in eight games, will likely see more minutes as well. Miller said forward Zach Peters, a transfer from Kansas who's battled concussion issues, isn't ready for consistent minutes.
Playing time among the players vying for minutes will likely be based on circumstance -- how well they're playing, the opponent and what the Wildcats need during specific points in games.
"If we did nothing different other than just give the players who have played, minus Brandon, more of an opportunity, that's part of our solution," Miller said. "With that in mind, we know foul trouble and fatigue can certainly weigh against you, but we don't have to do this for 30 games, just nine regular-season games and then we're in the postseason."
Arizona's stretch run without Ashley starts Thursday night at home against Oregon.
Information from The Associated Press was used in this report.