The Mexican striker scored from close range after five minutes and he latched on to a Ryan Giggs pass to double the lead 15 minutes from time.
United defender Wes Brown headed an own goal with eight minutes left to ensure a nervy finale but the Premier League leaders survived to advance 2-1 on aggregate.
"We are delighted, it was a difficult game," United striker Wayne Rooney told Sky Sports. "We knew they were a big physical team but I think we deserved it in the end."
United, under pressure not to concede following a 0-0 draw in the first leg in Marseille, started strongly and were rewarded when Rooney's pinpoint cross found Hernandez who turned the ball into an empty net.
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Without their injured captain Nemanja Vidic, United coped comfortably with Marseille's attack and Rooney and Hernandez enjoyed plenty of possession without creating many clear chances.
The French side worked tirelessly after halftime and pinned the home team back but they lacked the craft to threaten Edwin van der Sar's goal.
Substitute Antonio Valencia created the second United goal with a deft through ball to Giggs whose neat cross was gleefully swept home by Hernandez.
Marseille refused to lie down and they were rewarded when Brown headed a corner into his own goal and Paul Scholes was unable to stop the ball crossing the line.
But United kept their shape well in the closing minutes and remained on course for their fourth European Cup and a treble of trophies this season.
