Long, who also defeated Michael Smith at the tournament in 2023, capitalised on missed doubles by Rock to claim another notable victory on the Madison Square Garden stage.
After Rock recovered from 3-0 down to level at 3-3, the Canadian won three of the next four legs to seal his place in the quarter-finals.
“It’s an amazing feeling to win on this stage. I’m over the moon,” Long said.
“I’ve played Josh three times on the tour, so we’re familiar with each other, and I was fortunate he missed a couple of doubles at the end there.
“I just want to play every game I can play and perform at my best with every chance I get.”
Long's reward is a meeting with Luke Littler, who recovered from 4-3 down to beat David Cameron 6-4 after an unconvincing start.
Humphries, meanwhile, opened his bid for successive US Darts Masters titles with a comfortable 6-1 victory over Leonard Gates.
“This is a really prestigious event and one of the best venues in the world,” Humphries said.
“My brother told me in the last eight events I’ve played in -- including the Premier League -- I’ve made eight finals on the trot, so that’s given me a lot of confidence.
“I’ve been a really tough player to beat in the last few weeks, and it’s nice to have that winning feeling back.”
Humphries will face Stephen Bunting in the quarter-finals after the Merseyside native defeated Alex Spellman 6-2.
Elsewhere, Gian van Veen marked his US Darts Masters debut with a 6-1 triumph over Fred Krueger and will play Jonny Clayton, who beat Gary Mawson 6-2.
Gerwyn Price also progressed with a 6-4 win over Brayden Hall and will face James Wade, who bettered Adam Sevada 6-3 on his return to the World Series circuit.
Results
Gian van Veen 6-1 Fred Krueger
Gerwyn Price 6-4 Brayden Hall
James Wade 6-3 Adam Sevada
Jim Long 6-4 Josh Rock
Luke Littler 6-4 David Cameron
Luke Humphries 6-1 Leonard Gates
Jonny Clayton 6-2 Gary Mawson
Stephen Bunting 6-2 Alex Spellman