Trinity were outclassed and out-muscled by Hull KR, who are many peoples’ predictions for relegation favourites.
Ex-Castleford Tigers winger Ben Crooks scored four tries as they eventually pulled away on an emotional night at Hull College Craven Park.
Brough, 37, suffered a knee injury in the first period but battled on until half-time.
He returned for the second period but was clearly not fit and limped off in the 54th minute.
Wakefield had already lost England centre Reece Lyne to a head knock but only trailed 14-6 when ex-Man of Steel Brough departed.
Dismayed boss Chris Chester admitted: “It doesn’t look great and it is potentially an ACL.
“He did it towards the back end of the first half and thought he could run it off but it doesn’t look great now for Broughy.
“He’d been looking really fit in pre-season and I do feel for him.
“Losing Reece as well had an effect on us on that right edge and in many ways it is the worst possible start to the season but we can’t feel sorry for ourselves.”
Trinity made a succession of errors throughout and wasted numerous chances, particularly in the first half when Ryan Hampshire bombed one great opportunity.
As Hull KR’s squad warmed-up with ‘Mose 10’ emblazoned on their training tops, it was just another reminder of what they are fighting for.
Their team-mate Mose Masoe remains in hospital after suffering a serious spinal injury against Wakefield last month and - still uncertain if he will ever walk again - the squad has pledged to play this campaign in his honour.
This gutsy if messy performance certainly suggested they will battle hard for him but Trinity’s effort was questioned by their boss.
Debutants Joe Westerman and Josh Wood scored Wakefield’s tries, one in each half, but there was little else to cheer.
Ryan Brierley rounded off the KR win and ex-Castleford winger Greg Minikin also scored on debut with Jamie Ellis kicking three goals.
Chester said: “It was very very disappointing, the effort of some individuals tonight.
“We always knew it’d be an emotional night for obvious reasons.
“We had a glimpse a couple of weeks ago how they'd play but we got out muscled.
“I was really disappointed with the errors; there was 16 with the Rocky Hampshire one right at the end and you can’t win with that many mistakes.
“Coming in to half-time, though not playing particularly well, we gave ourselves a decent chance.
“But we had guys making stuff up and we looked like a group of players just thrown together.
“As a coach we have to have a look at some real uncharacteristic errors from Tom (Johnstone), Broughy and Hampshire.
“I’m expecting a big reaction next week. We were just miles off tonight."
Hull KR: Quinlan; Minikin, Kenny-Dowall, Linnett, Crooks; Ellis, Brierley; Lawler, Litten, Murray, Livett, Storton, Abdull. Substitutes: Mulhern, Garbutt, Maher, Minchella.
Wakefield Trinity: Hampshire; Atkins, Lyne, Tupou, Johnstone; Miller, Brough; Kopczak, J Wood, Tanginoa, Pitts, Ashurst, Westerman. Substitutes: Kirmond, Navarrete, Tangata, K Wood.
Referee: Robert Hicks (Oldham)