Centre Senior, 33, became the first player in the modern era to reach the landmark figure when he led out Brian McClennan's reigning champions.
And he scored one of his side's seven tries as the Rhinos condemned Hull to a 12th defeat in their last 15.
But the home side deserved every credit after recovering from 30-6 down at one stage.
The two points, earned without injured playmaker Danny McGuire, represented Leeds' fourth straight win - and their seventh in their last eight outings.
Victory also brought them to within two points of table-topping Saints, who fell to a shock 20-10 defeat at Salford on Friday.
McClennan said: "I'm pretty happy with that. We knew once we got the ball, we could do something with it.
"Both teams really attacked well and put on some good plays, but we know we can defend better than that.
"It is important to consolidate our position. It was a really good effort and we're really proud of Keith's 500 games in the pro era."
Hull, who came into the game buoyed by the signing of Australia Test forward Mark O'Meley, soon had their bubble burst as Leeds produced a stunning first-half performance.
The procession started as early as the fifth minute when Senior fed England winger Ryan Hall for his 20th try of the season.
Hull had reason to feel aggrieved by the score as there appeared to be a forward pass in the build-up, while there was also some suspicion that Hall had stepped into touch.
Leeds did not let it affect them, though, and Hall went over again three minutes later after excellent work from Senior and Kevin Sinfield.
Hull briefly fought back, with Shaun Berrigan powering over while Danny Tickle added the goal to extend his run of being the only player to score in every game this season.
Tickle went on to add a try and a goal before the break and Willie Manu had one chalked off by the video ref - but not before Leeds had posted another three scores.
Senior was the first to go over, blasting his way past Graeme Horne for a 230th career try.
Scott Donald then bagged his sixth score of the season while Sinfield, who converted all five of the tries from the touchline, went in for a deserved four-pointer of his own.
The points continued to flow after the break as Gibson plundered a score in the corner, allowing Sinfield to maintain his stunning record.
Hull did manage to stem the flow and mounted a stirring comeback with a brace of tries from Gareth Raynor and Kirk Yeaman, with Tickle converting both.
Rob Burrow then dropped a goal to earn Rhinos a three-score lead, before Hull's Mike Burnett crossed.
But Leeds finally put Hull's resilience to bed with a try from Lee Smith which Sinfield converted.
Hull coach Richard Agar said: "We can take plenty out of it and we spoke about passion and commitment. Our heads could have gone down after 15 minutes, as a couple of big things didn't go for us."
SCORERS - Hull: tries Berrigan, Tickle, Raynor, Yeaman, Burnett; goals Tickle 5. Leeds: tries Hall 2, Senior, Donald, Sinfield, Gibson, Smith; goals Sinfield 7; drop-goals Burrow.
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