Early in the first quarter of Sunday night's clash at Marvel Stadium, Wanganeen-Milera handballed to teammate Max Hall, attempted to burst away then grabbed at his hamstring as he tried to receive the ball back.
A dejected Wanganeen-Milera limped straight down to St Kilda's rooms and the deflated Saints never looked in the match, losing 15.10 (106) to 8.14 (62) as Carlton tightened its grip on a wildcard berth and the head coach role became Josh Fraser's to lose.
The 23-year-old re-emerged but shuffled to the bench and sat in the back row, banging the glass behind him in frustration, before later having an ice bag strapped to his thigh.
Even a standard hamstring injury would rule Wanganeen-Milera out of St Kilda's remaining games against Richmond and Gold Coast.
Veteran Mason Wood was ruled out with a calf injury late in the second quarter, which could finish his season too.
Ahead of the game, 10th-placed Carlton were just one win clear of Ross Lyon's 11th-placed Saints.
The victory takes Carlton (44 points) to 10 wins from 12 matches under interim coach Fraser, eight points clear of the chasing pack of St Kilda, GWS and North Melbourne (all 36).
Fraser is expected to throw his hat into the ring for the fulltime role this week, ahead of Carlton's clashes with the Western Bulldogs (48 points) and leaders Fremantle, and appears an almost unbackable favourite.
Carlton fans chanted "we want Fraser" in the final minutes of the match.
Wanganeen-Milera was under an injury cloud all week, missing Thursday's training as he battled a hip issue suffered in last week's loss to Sydney - but was ultimately cleared to play.
The 23-year-old averaged 30 disposals, a goal and a direct goal assist this season, but has been red hot recently, including kicking four goals and notching 46 disposals against North Melbourne.
Apart from Wanganeen-Milera and Hill, the Saints had more injury scares.
Liam Ryan (left shoulder), former Blue Tom De Koning (right shoulder) and Bradley Hill (left knee) went down to the rooms but returned to play.
Carlton led a deflated St Kilda by 25 points at halftime and 35 at three-quarter time.
Harry McKay kicked three goals while dominant ruck Marc Pittonet, Will Hayward, Mitch McGovern, Brodie Kemp and Ben Ainsworth kicked two apiece.
Francis Evans (21 disposals, nine score involvements) was superb, Patrick Cripps (26 disposals), George Hewett (26) and Sam Walsh (26) got the grunt work done and Adam Cerra and Ollie Florent provided class.
Hall (30 disposals, 10 clearances, two goals) and Hill (31 disposals) were the most influential Saints, while Mitch Owens kicked 2.2 and Jack Higgins finished with 1.4 on a tough night.
Former Blues Jack Silvagni and De Koning were booed early in the match by Carlton fans.
