Clayton produced another clinical display to cap an impressive night, adding the Nottingham title to his earlier success this season and strengthening his position at the top of the table.
The Welshman had already come through Michael van Gerwen and Stephen Bunting to reach the final before overpowering Humphries in a one-sided decider.
The final turned quickly in Clayton's favour. He broke throw in the opening leg after Humphries failed to take out 140, then moved 2-0 ahead when a heavy scoring burst left double 12 and Humphries missed double 16 for a 106 finish.
Humphries responded with a fine 121 checkout to get on the board, but Clayton immediately reasserted control and never allowed the match to become competitive.
The key moment came in the fifth leg. Humphries had reduced his finish to 140 and, with Clayton back on 283, looked well placed to hold. Instead, after setting up 80, he missed tops and Clayton punished him with a superb 146 checkout for a double break.
Clayton then moved 5-1 ahead and then wrapped up the victory on double 16 after Humphries again struggled with his finishing.
Both averaged just shy of a ton in the final, with Clayton hitting a clinical 66 per cent of his doubles to Humphries' 12 per cent.
The result extends The Ferret's lead at the top of the table, with the world number five - who was limping throughout the evening - sitting on 19 points after just six weeks, eight ahead of Luke Littler in second place.
'Tonight was a bit difficult'
"I wasn't expecting much tonight," Clayton told Sky Sports afterwards.
"I suffer from gout in my ankles, and tonight was a bit difficult with the way I walked. My arm was okay, by the looks of it, and that's all that counts.
"I was practising just to keep on it, as every time I sat down, it stiffened up. It's the most I've ever practised. I am dreading taking my shoe off.
"Everybody is nicking points off everybody, so I didn't expect to be top of the league after Night Six. I was hoping to have eight points all told.
"It is great to get points on the board early. It is my favourite tournament, and my darts are doing the talking."
Humphries shows signs of life
Humphries had reached the final with a dramatic 6-5 win over Littler in the semi-finals, ending a run of five defeats against the world number one.
The match was tight throughout before Humphries produced a high-class 128 checkout in the deciding leg, landing two treble 18s before pinning double 10 to progress.
Earlier in that contest, he had also taken out 130 and produced an 11-dart break, while Littler stayed in touch despite trailing 5-2, but Cool Hand Luke rode out the match to victory despite some distractions from the crowd.
Littler and Price put on show
Littler had opened his evening with a hard-fought 6-5 quarter-final victory over Gerwyn Price in one of the matches of the night.
Price produced back-to-back ton-plus checkouts of 151 and 152 during a stirring fightback, but Littler held on in the decider to maintain his recent run of form following his nightly win in Cardiff and his UK Open triumph.
Littler averaged an emphatic 108 against Price, who himself was north of a ton in defeat.
Clayton's route to the final began with a 6-3 win over Van Gerwen. After losing the opening two legs, he recovered strongly and won six of the next seven to continue his perfect quarter-final record this season.
He then beat Bunting 6-3 in the semi-finals, pulling clear in a match that had briefly been level at 3-3 before a crucial break of throw put him in command.
Humphries, meanwhile, booked his place in the last four with a 6-4 victory over Gian van Veen.
Although there were signs of the finishing inconsistency that has troubled him at times this season, he found the key doubles when it mattered and recovered well after a patchy start.
The opening match of the night saw Bunting beat Josh Rock 6-1, with Rock's difficult Premier League campaign continuing as he suffered a sixth consecutive defeat, with missed doubles once again proving costly.