The 2023 champion missed 14 darts at double in the opening set but still won it 3-1, finishing on double one.
He then took the second set by the same score, which included a 109 checkout on double 16.
Chisnall had a chance to break in the final leg but busted on 101.
Humphries plays Jermaine Wattimena on Thursday.
Dobey and Rock join fallen seeds
Wattimena knocked out 15th seed Chris Dobey 2-0 in the evening's first match, finishing with a 134 followed by 40 on tops in a last-leg decider.
Dobey averaged 79.93 and missed 19 darts at a double to start legs. He reached the quarter-finals in 2022 and 2023 but has now lost in the first round for three consecutive years.
Seventh seed Josh Rock also went out, beaten 2-1 by debutant Niels Zonneveld. Rock was a leg from defeat in the second set when he hit a 180 and checked out 151 to force a decider.
Zonneveld then won the final set 3-1 with finishes of 103, 116 and 133, the last of them on his favoured double 14. Rock has lost his opening match at every World Grand Prix he has played, bar one.
Anderson survives against Heta
Zonneveld will face Gary Anderson, who beat Damon Heta 2-1 after the Australian missed a match dart at double five. Heta had won the first set and hit a 156 checkout in the second.
Anderson levelled the match with a 115 finish and won the deciding set 3-0, which leaves Heta without a win in six appearances at the event.
Gian van Veen beat fellow Dutchman Dirk van Duijvenbode 2-0, winning the match with a 69 checkout on double 16 moments after Van Duijvenbode had missed the same double for a break.
Van Veen plays Ryan Searle, who beat William O'Connor 2-1 after trailing 2-0 in the final set.
O'Connor had won five legs in a row, then missed the bull for the match on 126, and Searle won the next three legs.
James Wade survived six missed match darts to beat Joe Cullen 2-1. Cullen took the first set 3-1, and Wade levelled with an 81 checkout on the bull before winning the decider on double 10.
He will play Stephen Bunting, who beat Andrew Gilding 2-1 in the last match of the night and finished on double eight after hitting a 180.