Calvin McCarty and Kerry Joseph also scored touchdowns for Edmonton against the Ticats, who dropped a 43-13 decision in Montreal on Sunday.
Chris Williams and Avon Cobourne scored touchdowns for Hamilton.
Edmonton quarterback Ricky Ray was 25-of-32 passing for 227 yards, one touchdown and no interceptions. Ray hooked up with slotback Fred Stamps 11 times for 130 yards.
Hamilton kicker Justin Medlock was 3-for-3 on field-goal attempts, hitting from 29, 40 and 45 yards. Edmonton's Derek Schiavone was good on 3-of-4 tries, hitting from 11, 27 and 26 yards but missing wide left from 28 yards.
Edmonton (7-4) moved into a tied with Calgary for top spot in the West, but the Stampeders still have a game in hand.
Hamilton (5-6) entered the game as the league's second-leading offence behind Montreal and were tied for the league-best with a 4-1 record at home.
The Tiger-Cats have clearly been hurt by the loss of veteran centre Marwan Hage, who has missed the past two games. Hamilton entered Friday second in the league behind Montreal for the least sacks allowed (15) but gave up five in the loss to Edmonton.
Hamilton quarterback Kevin Glenn completed 14-of-23 pass attempts for 140 yards and one interception before being replaced by backup Quinton Porter with 11:26 left in the fourth.
An unhappy crowd of 22,654 sent the home team into the locker-room with a showering of boos at halftime as the Ticats trailed 25-6.
But that changed 14 seconds into the third quarter when Williams returned the kickoff 93 yards for a touchdown.
The TD put the crowd in a better mood, but did little to change the momentum. The teams traded field goals before the third quarter ended with Glenn's interception by Edmonton defensive back Chris Thompson, who ran it 53 yards to the Hamilton 15.
The Hamilton defence looked to have stuffed Edmonton at the one-yard line, and recovered a fumble, but a couple offside penalties gave Edmonton a second and third chance. When an Edmonton time count violation moved the ball back, that gave Messam the room he needed for a six-yard TD run and the 35-16 lead. A Schiavone 26-yarder made it 38-16.
Porter orchestrated a 91-yard scoring drive late in the game that ended with a six-yard TD run by Cobourne to make it 38-23.
The game was tied early 3-3 before Edmonton's offence took over. Messam rushed for 102 yards on eight carries in the first half alone, while Stamps was the receiver of choice, with 111 yards on nine catches.
Ray led a 70-yard drive, culminating in Messam's 26-yard touchdown run up the middle for a 10-3 first-quarter lead.
Late in the quarter, Glenn dumped the ball off to Cobourne for a short gain, but he fumbled and the ball was recovered by former Ticat Jykine Bradley at the Hamilton 40. That began a scoring drive that ended with Ray's seven-yard TD pass to McCarty early in the second quarter to make it 17-3.
A 15-yard no-yards penalty against Hamilton gave Edmonton the ball on the Ticat 45. On the next play, Messam ran it 43 yards to the Ticat two-yard line to set up Joseph's one-yard TD run to make it 24-3.
A missed field goal by Schiavone and Medlock's 40-yarder made it 25-6 heading into halftime.
Notes: The Eskimos have beaten Hamilton in both meetings this season, having also won 28-10 at home in Week 2. Edmonton hadn't won at Ivor Wynne since 2008.