Tedesco scored two late tries dousing any thought of a Sea Eagles comeback, who are yet to record a victory under new coach Trent Barrett.
Between Tedesco and centre Kevin Naiqama, the duo combined for four tries and three try assists with the latter's passing prowess throughout the game well-received by the Tigers faithful.
The Sea Eagles early 2-0 lead was short lived when in the fifth minute David Nofoaluma's try sent the Leichhardt hill into raptures.
A Nate Myles error allowed Luke Brooks to regather his own kick, who quickly threw it to halves partner Mitch Moses. Throwing caution to the wind - on the zero tackle - the five-eighth's decision to kick to an open Nofoaluma proved the best course of action.
Naiqama kept the good times rolling midway through the first half when he sliced through haphazard Sea Eagles defending to score out to the right.
Three minutes later Naiqama proved the impetus for the Tigers' third try when he forced his way through more ordinary Sea Eagles defence before sending Tedesco away to score his first.
Manly back-rower Lewis Brown provided some relief for coach Barrett when he forced his way over from dummy half in the 32nd minute.
Dylan Walker ensured the Sea Eagles entered half-time down by only six points when he palmed off Moses and Kyle Lovett in a solo scoring effort three minutes from the break.
Jorge Taufua crashed over in the corner in the 42nd minute, and with Jamie Lyon's clutch sideline conversion, gave the Sea Eagles equal pegging in the second half.
The Tigers remained unperturbed however and in the 50th minute Jordan Rankin scored his first try as a Tiger – the home side handed good field position thanks to an ugly tackle by Martin Taupau on his former teammate Moses minutes earlier.
Magic hands from Naiqama again helped winger Nofoaluma to his second of the game in the 59th minute, taking the Tigers to an eight-point advantage heading into the final quarter. Moses extended the lead to 10 with a 64th minute penalty goal.
Tedesco screamed through a gaping hole in the Sea Eagles' defence to score his second try before Taupau's 74th minute try gave Manly a glimmer of hope.
But it was quickly shut down with Tedesco securing his hattrick two minutes from full-time to seal the win.
Wests Tigers 36 (James Tedesco 3, David Nofoaluma 2, Kevin Naiqama, Jordan Rankin tries; Mitch Moses 4 goals) defeated Manly Sea Eagles 22 (Lewis Brown, Dylan Walker, Jorge Taufua, Martin Taupau tries; Jamie Lyon 3 goals) at Leichhardt Oval. Crowd: 11,269. Half-time: Wests Tigers 16-10. Injuries: Curtis Sironen (Wests Tigers) – hamstring.