Suarez was making his first appearance of the season following the completion of his 10-match ban for biting Chelsea's Branislav Ivanovic in a Premier League clash last term.
But the controversial Uruguayan's presence in the Liverpool starting line-up wasn't enough to galvanise his team to victory at Old Trafford as Hernandez bagged the winner for United less than two minutes into the second half.
David Moyes's team were on course to bounce back from Sunday's painful 4-1 derby defeat at Manchester City, and also avenge a 1-0 loss against Liverpool in the league this season, when Wayne Rooney's corner picked out the unmarked Hernandez to volley home in the 46th minute.
Suarez, who had angered Liverpool with his failed attempt to engineer a move to Arsenal during his suspension, hit the bar with a free-kick in the closing stages and also went close when his powerful strike rippled the side-netting, but United held on to move into the fourth round.
"The movement is great for the goal, that's what Chicharito (Hernandez) is all about. He finds space so well," Moyes said. Liverpool manager Brendan Rodgers added: "I can have no complaints. One lapse of concentration has cost us.
"I thought Luis Suarez was excellent. You could tell he'd been out for a long time as he tired at the end. But he's obviously a threat." Arsenal's young guns held their nerve to win 4-3 on penalties after 1-1 draw at West Bromwich Albion.
Denmark forward Nicklas Bendtner returned to the Arsenal team for the first time in more than two years as manager Arsene Wenger made nine changes, giving game-time to a host of youngsters.
Wenger's side took the lead when Bendtner's defence-splitting pass gave Thomas Eisfeld a clean run on goal and the German youngster slotted home in the 61st minute.
But Burundi-born England Under-21 striker Saido Berahino rose to head the equaliser from Steven Reid's cross 10 minutes later.
In the shoot-out, Arsenal's German teenager Serge Gnabry saw his spot-kick saved by Luke Daniels, but Craig Dawson and Morgan Amalfitano both missed the target for Albion and Nacho Monreal drove in the winner.
League Cup holders Swansea suffered an embarrassing exit as Championship side Birmingham won 3-1 at St Andrews.
Michael Laudrup's side routed Bradford at Wembley last season to clinch the first trophy in the Welsh club's 100-year history.
But Laudrup made 10 changes from the line-up that beat Crystal Palace in the league on Sunday and their defence of the trophy ended at the first attempt.
On-loan Fulham centre-half Dan Burn headed Birmingham in front in the 57th minute before striker Matt Green, who was playing non league football with Mansfield last season, got across his marker to slide in a Chris Burke cross four minutes later.
Tom Adeyemi added the third in the 81st minute and Wilfried Bony's stoppage-time strike was no consolation for Swansea. Newcastle eased through with a 2-0 win over Championship side Leeds at St James' Park.
Leeds manager Brian McDermott was given his first break in coaching by Newcastle boss Alan Pardew when he was in charge at Reading in 2000.
But there was little chance of Pardew being so accomodating this time, even though the Magpies fielded a team featuring six changes.
The hosts went ahead when Senegal striker Papiss Cisse ended his 11-game goal-drought with a header from Shola Ameobi's cross in the 31st minute for his first goal since April.
And French midfielder Yoan Gouffran sealed the victory as he smashed in a powerful shot from the edge of the area for his first goal for the club in the 67th minute.
Stoke midfielder Stephen Ireland scored his first goal for the club in a 2-0 win over League One strugglers Tranmere Rovers
Rovers are currently 19th in the third tier with just one win so far this season and Mark Hughes' men were always in control at Prenton Park.
Ireland was handed his first Stoke start as Hughes made seven changes and the on-loan Aston Villa midfielder opened the scoring in the 23rd minute, collecting a through ball from Marko Arnautovic before slotting home for his first goal since December 2011.
Former Liverpool and Tottenham striker Peter Crouch notched the second in the 90th minute.