Premiership champions Harlequins were taken all the way by Worcester, who grabbed two late bonus points as compensation for losing at The Stoop.
Quins looked comfortable at 21-3 up at half-time with tries from Louis Lynagh, Alex Dombrandt and Cadan Murley.
Joe Marchant cancelled out a try from England centre Ollie Lawrence for Worcester who crossed again through Willi Heinz and Will Chudley.
But after Quins' Dino Lamb-Cona scored, Warriors' Mark Thomas got the last try.
That was worth two bonus points - one as it was Warriors' fourth try, and a second for losing by only six points.
Tommy Allan had a great day with the boot for the hosts, landing all five conversions, including three from the touchline, while Owen Williams kicked three of Worcester's four conversions and a penalty.
Quins rode their luck in their second successive bonus-point victory, after edging Newcastle in round one, but their scrum emerged as a key weapon.
New England squad member Lynagh also displayed his power and nose for the line by finishing the first try in front of the watching England coach Eddie Jones.
Lynagh, son of Australia great Michael Lynagh now faces a decisive autumn in his quest to win his first cap, according to new Harlequins boss Tabai Matson.
On Tuesday the 20-year-old wing, who is also qualified for Australia and Italy, was included in England's pre-autumn training squad for the first time and Matson believes November will be make or break for his Test prospects.
The Premiership's first woman referee
Sara Cox became the first woman to referee a Premiership game as she took charge of the fixture.
It was a delayed debut as she had originally been chosen to referee the Worcester-Gloucester game in June, which was cancelled because of Covid.
Cox, 31, from Devon, became the world's first professional female rugby union referee in 2016, and was the first woman to take charge of a game between two top-tier sides when Northampton beat Wasps in the Premiership Cup in 2018.
In her first league fixture in charge, she dished out one yellow card to Warriors winger Noah Heward for an aerial challenge on Tyrone Green.
Harlequins coach Tabai Matson:
"At the end of this (England) camp it will be really interesting to see if Eddie (Jones) thinks Louis Lynagh is going to be an international calibre winger. What you want from your wingers is the ability to finish and he's been prolific.
"He's got lots of things to work on because international rugby is another step up again. But every week he just puts up his hand. Every time he gets an opportunity, he takes it and that shows us a glimpse of what he's capable of in the future.
"To be fair, the Newcastle victory with a bonus point was more than we could have asked for and to scrape through against Worcester. In the first half, we felt like we had the game under control but you have to respect what Worcester did. They made it really difficult for us."
Worcester head coach Jonathan Thomas:
"We wanted to come here to gate-crash the party.
"Congratulations to Harlequins for their success last season. It was a great occasion.
"But we wanted to change the narrative of what the day was going to be about and we nearly did that."
Harlequins: Green; Lynagh, Marchant, Esterhuizen, Murley; Allan, Care; Marler, Walker, Kerrod, Symons, Lamb, Lawday, Kenningham, Dombrandt (capt).
Replacements: Riley, Baxter, Collier, Tizard, Chrisholm, Steele, Jones, Northmore.
Worcester Warriors: Shillcock; Heward, Lawrence, Venter, Humphreys; Williams, Heinz (co-capt); Waller, Baldwin, Judge, Hatherell, Clegg, Hill (co-capt), Lewis, Kvesic.
Replacements: Annett, M Thomas, Owlett, Garvey, Kitchener, Chudley, Searle, Nanai.
Sin-bin: Heward (35).
Referee: Sara Cox