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.
United manager Alex Ferguson bemoaned the loss of defenders John O'Shea and Rafael da Silva to hamstring injuries during the match following the withdrawal of his captain Nemanja Vidic before kickoff.
"It was nervy in as much as we lost two defenders in the game which upset our balance," Ferguson told Sky Sports. "The problem for us was their height and they were always a threat at set pieces."
United striker Wayne Rooney said his team had deserved to go through.
"We are delighted, it was a difficult game," Rooney said. "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.
Missing Vidic and Rio ferdinand, United coped comfortably with Marseille's attack and Rooney and Hernandez enjoyed plenty of possession without creating many clear chances.
Andre-Pierre Gignac and Soulemayne Diawara missed good chances to equalise and the French side worked tirelessly after halftime, pinning the home team back but lacking the craft to threaten Edwin van der Sar's goal.
Substitute Antonio Valencia created the second United goal with a deft through pass 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 towards 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.