American Isner landed 11 aces as he beat sixth-seeded compatriot Ryan Harrison 7-6(4) 6-3 while Hewitt overcame former champion Rajeev Ram 6-4 5-7 6-2.
Youngster Harrison pushed Isner throughout the first set, sticking with the top seed until the tie-break and even saving a first set point before double-faulting to hand his fellow American the set on the second attempt.
Isner had an easier time in the second set, breaking early before going on to seal his berth in the final after 86 minutes.
Hewitt, who will be playing in his first ATP Tour final in more two years, recovered from a break down in both the first and third sets as he survived 2009 champion Ram in two hours and 21 minutes.
“Early on in the match, I had a lot of break points, but he came up with big first serves,” said Hewitt, playing in his first ATP semi-final since Halle in 2010.
“It was a matter of if I got that small opportunity, with a second serve and a break point, I had to step up and take it.
“You come back from surgery and you think about everything. My whole mechanics have changed. So that’s taking a bit of time,” added Hewitt of his foot surgery in February.
The Australian has won all seven grass court finals he has played in his career.
“I’ve never beaten him before and I’ve never played him on grass,” Isner said of Hewitt. “It’s going to be a big challenge. It’s also going to be an honour sharing the court with him. He’s one of the guys I really, really respect.
“It’s good to see him back but I hope I can beat him tomorrow.”
The top two seeds, David Ferrer and Nicolas Almagro, will contest the ATP Bastad final after comfortable semi-final victories in Sweden, while Janko Tipsarevic progressed to his first career clay court final in Stuttgart.
World number five Ferrer's Indian summer continued with a 6-3 7-5 win over Grigor Dimitrov, putting the 30-year-old Spaniard into his sixth ATP Tour final of the year.
The 2007 champion completed his 50th win of the season in just over an hour and a half, after taking defending an early break in the first set before saving two set points in the second.
Last year’s runner up, Ferrer followed that with a break and a hold against the Bulgarian sixth seed, setting up a final clash against compatriot Almagro after he beat Jan Hajek of the Czech Republic 6-4 6-3.
"I didn't serve well today," said Ferrer. "I saved good points and I was a bit lucky in the (second) set. I'm very happy to be in the final here in Bastad.
"I have played (Almagro) many times before and I know I will have to run a lot on the court."
Almagro, the 2010 champion, put eight aces past Hajek as he qualified for his fourth final of the season.
The 26-year-old, who lost to Ferrer in the 2007 final, has won titles in Sao Paulo and Nice this year.
In Stuttgart, Serbian star Tipsarevic beat Brazilian Thomaz Bellucci 6-4 2-6 6-4 in two hours and three minutes.
The world number eight moves into his first final of the season, where he will face second seed Juan Monaco.
The Argentine needed two hours and 41 minutes to beat Guillermo Garcia-Lopez 6-3 3-6 7-5, his fourth consecutive defeat of the Spaniard.
Garcia-Lopez had battled back from 5-1 down to level in the deciding set, but was broken late to lose.
At the ATP Umag event in Croatia, top seed Fernando Verdasco lost to fellow Spaniard Marcel Granollers 6-2 6-7(5) 6-1 in the first semi.
The match lasted almost three hours and means that world number 24 Granollers enters his first final of the season.
Fourth-seeded Granollers will face second-seeded Marin Cilic of Croatia in Sunday's final after he beat Ukrainian third seed Alexandr Dolgopolov of Ukraine.