Edmund advanced by beating 54th-ranked Serb Miomir Kecmanovic 6-4 6-1 in a Saturday afternoon semi-final at the Nassau Coliseum on Long Island.
Seppi prevailed in the nightcap when he outplayed 131st-ranked Jason Jung of Taiwan 6-3 6-2.
Edmund and Seppi have clashed five times, most recently in Auckland in January, when the Briton won in straight sets to improve his record against the Italian to 4-1.
Edmund's lone career title came at Antwerp in 2018, while 35-year-old Seppi has three career titles, but none since 2012.
"This is great to be back in a final, playing the matches you want to be playing," Edmund said after making quick work of 62nd-ranked Kecmanovic in a match that lasted barely an hour.
"I obviously want to go all the way, but I'm enjoying my tennis. I've kept improving and learning with each match."
In the other semi, Seppi eventually wore down a stubborn Jung, who was particularly vulnerable on second serve.
The 98th-ranked Seppi converted five of his 13 break opportunities for an ultimately comfortable victory.