Humphries battled past four challengers to claim the trophy, first beating Stowe Buntz 6-4 in the opening round before going on to defeat Danny Lauby Jr. (6-2) and Gerwyn Price (7-2) ahead of the final showdown with Aspinall.
'Cool Hand' averaged an impressive 99.14 during the clash with his fellow Englishman while 'the Asp' lagged slightly behind with an average score of 92.49.
The world number one started strongly by racing into a 5-2 lead before Aspinall eventually levelled up at 6-6.
Humphries then powered back to seal the title with an 8-6 victory, hitting four 180s throughout the match.
"(Madison Square Garden) is the most iconic venue that we play in and it's really special to win this event," said Humphries.
"It's one of the top venues in the world and it's one I've always dreamed of winning. When I finally won it tonight, it was an amazing relief.
"Once I knew I was in a winning position, I started getting nervous - I'm really pleased to win and I'm over the moon. It's another massive event ticked off for me.
"I've won World Championships, World Matchplays, Premier Leagues and these big titles and it felt like I'd won another major.
"That's how big it is - it's very special and you could see my relief at the end. This was the one on the World Series that I really wanted to win."
The win was Humphries' second on the PDC World Series of Darts circuit, which continues with the Superbet Poland Darts Masters next weekend.