It was Littler's first appearance on the European Tour since March's Belgian Darts Open, and he wasted little time shaking off any rust.
He opened with a 108.59 average against Niko Springer, a repeat of their World Matchplay meeting in July, before edging past Krzysztof Ratajski 6-3.
A 6-0 whitewash of Danny Noppert in the quarter-finals, in which he averaged 102.48, sent him through to a semi-final against Michael van Gerwen that he won 7-3 at 106.64, a display that featured an 11-darter, a 167 checkout on the bull and a 76 finish.
That set up a final against Humphries, the man Littler had partnered to World Cup glory, and a rematch neither side had contested on the European Tour before.
It took a while to get going, until Humphries nailed checkouts of 110, 88 and 92 to move 3-2 up, and an 11-darter in the seventh leg looked to have him in control.
Littler had other ideas, reeling off back-to-back 12-darters, the second finished with a 130 on the bull, to turn a losing position into a 7-4 lead.
Humphries responded with a second 11-darter of the match hauled him back to 7-6, but with the finish line in sight he missed two darts at double 16 that would have forced a decider.
Littler made him pay, finding double 10 to seal it.
Both men finished with strikingly similar numbers, Littler averaging 95.25 to Humphries' 94.81, testament to how tight the contest had been despite the scoreline suggesting otherwise.
"It was a good game," Littler said afterwards. "This is what the fans are in for, me and Luke are back. The two best going at it in a final once again.
"I'm glad I've won. It's good to be back and I'm back with a bang.
"These long days are worth it, especially lifting the trophy. I think I've secured my place in Dortmund. Dortmund is the one I'm chasing."
That win also confirms his spot at next month's European Championship in Germany.
Humphries had come close to missing the tournament altogether. The world champion revealed he had considered withdrawing on Thursday because of an injury concern, only to fight through to a fourth final in his last five European Tour outings.
His route to Sunday included wins over Beau Greaves, whom he beat with an average just shy of 109, Andrew Gilding, William O'Connor in the quarter-finals (6-3) and Gerwyn Price in the semi-finals, a 7-4 win built on checkouts of 105, 104 and 119 before Price rallied to 5-4 and Humphries shut it down with 71 on tops. He left Prague with the £15,000 runner-up cheque.
"It's been a great run for me, making four out of five finals," Humphries said. "I was going to pull out on Thursday, and I made the final, so I can't be too upset with myself because I did really well. I'm happy that I've had a good run and come back to see these amazing people, the fans, they're just amazing. That's why I'll be here every year.
"It's my favourite Euro Tour on the calendar. They're so respectful, it's amazing. I never give up, especially in finals.
"I know that Luke is obviously going to throw everything at me, that 130 was a big shot. Hopefully over the next four months I push him. If he does the clean sweep, he has to do it the hard way."
Elsewhere in Prague, Price reached the last four with a 6-1 rout of Cameron Menzies before beating Hungarian Darts Trophy champion Ross Smith in the quarter-finals.
Van Gerwen needed a comeback of his own to beat Wessel Nijman before seeing off Jonny Clayton to reach his first European Tour semi-final since March.
Noppert produced the result of the day in the earlier rounds, hitting seven maximums as he came back from 4-0 and 5-3 down to beat Luke Woodhouse, while O'Connor needed a deciding leg to see off Josh Rock at the same stage.