Vainikolo moved to Gloucester from the Bradford Bulls in June
Leeds Carnegie: (19) 24
Tries: Dunbar, Rock
Con: Di Bernardo
Pens: Di Bernardo 3, Brooks
Gloucester: (18) 49
Tries: Simpson-Daniel, Balshaw, Vainikolo 5, Allen
Cons: Lamb 3
Lesley Vainikolo had a dream debut following his switch from rugby league, scoring five tries as Gloucester thrashed newly promoted Leeds.
Vainikolo barrelled through several Leeds defenders for his first-half opener and scored four tries in 19 minutes in the second half.
Leeds, who suffered injuries to Alberto Di Bernardo and Hendre Fourie, scored tries through Jon Dunbar and Tom Rock.
The home team led 19-18 at the break but had no answer to Vainikolo.
The 28-year-old Tongan played league for the Bradford Bulls and several of his former team-mates were in attendance to watch him make his Premiership debut.
Vainikolo's last appearance for the Bulls was at Headingley Carnegie in June, when the winger scored in Bradford's 38-14 win over Leeds Rhinos.
His display for Gloucester hinted at a highly successful transition and he becomes the first player to score five tries on his Premiership debut.
Vainikolo, nicknamed the Volcano, was into the action after just three minutes, collecting a pass on the left-hand touchline and engaging on a typically aggressive run.
Dunbar scored a first-half try for Leeds
Gloucester won a penalty and switched play to the right flank, with Leon Lloyd's offload sending James Simpson-Daniel over in the corner.
Leeds responded with a superb passage of play and were rewarded when hooker Rob Rawlinson passed to Dunbar 20 metres out - the flanker charging down the left side before crossing.
Iain Balshaw responded for Gloucester before Vainikolo scored his first try as Gloucester took a slender lead into the interval.
Anthony Allen extended their lead after the break, but Rock brought Leeds back into the game before Vainikolo took over.
He showed great power for his second and third tries, then grounded a high kick for his fourth and crossed virtually unopposed for his fifth.
Gloucester's Lesley Vainikolo on his sensational debut:
"Only the man above can predict these kind of things and thanks to him, I had the power and strength to score.
"Credit to my team. The forwards did the hard yards and the backs finished.
"I was just concentrating on the way I want to play. I didn't think I was going to get that many tries."
Leeds director of rugby Stuart Lancaster:
"I've seen Lesley do that to world-class defences and he did it to us.
"To make this impact in his first game of union is very, very impressive. Credit to him and Gloucester for creating and taking those chances.
"They played well but we competed well across the park and have got lessons to learn and lots of positives to take."
Gloucester director of rugby Dean Ryan:
"The space that Lesley can create is the factor we're keen to exploit.
"His scoring is fantastic but his creating space for others is something we're coming to terms with as a team.
"We knew straight away that he has things that other players don't have."
Leeds: Goodridge; T Rock, Hepworth, Welding, Biggs; Di Bernardo, Bedford; Cusack, Rawlinson, Noon, Hooper, Myall, Dunbar, Fourie, Oakley.
Replacements: Hopcroft, Parkes, Bouza, M Lock, Brooks, Holtby, Hinton.
Gloucester: Balshaw; Simpson-Daniel, Lloyd, Allen, Vainikolo; Lamb, Prendergast; Collazo, Azam, Nieto, Pendlebury, Brown, Buxton, Hazell, Narraway.
Replacements: Titterrell, Califano, Tuohy, Strokosch, Lewis, Mercier, Morgan.
Referee: D Rose (RFU)