However, Irwin later cut the deficit to the leader but was passed by brother Andrew (SYNETIQ BMW) before he had a chance to make a move on Hickman for the lead.
As tire wear came into play, Hickman managed to keep his nose ahead as the Irwin brothers and Danny Buchan (SYNETIQ BMW) battled for second place.
It was Buchan who came to chase after Hickman, the Irwin brothers backing up.
MCAMS Yamaha’s Jason O’Halloran was on the move and joined the fight for the final grandstand spot.
The Australian passed Andrew Irwin to take fourth place and also briefly edged out Glenn Irwin, who fought back to regain position on the brakes.
O’Halloran, however, appeared to have more in the tank at the start of the final lap, but his race ended abruptly following contact from Andrew Irwin, causing him to crash unscathed.
Irwin continued in the race and finished in eighth place, but was later demoted to 17th after receiving a 20 second equivalent time penalty for the incident involving O’Halloran at Surtees.
Hickman’s advantage over Buchan at the finish was 0.6 seconds as the FHO Racing BMW team toasted their first win of the season.
“I’m so happy for Faye [Ho, owner FHO Racing Team] because the boys worked really hard and it’s nice to reward them with a win,” said Hickman, who finished second in Saturday’s race behind Irwin.
“It was a completely dry race, everyone was on the grid and I’m super, super happy.
“I don’t have a lot of goals in life or in my career, but one of the things I really wanted to do was win a big bike race at the TT and a British Superbike race in the same year, and we just done it.”
Ulsterman Irwin is now on course to secure second place in the BSB Showdown in Sunday’s final race after Tommy Bridwell was forced out of the pit lane due to a problem with his Oxford Products Ducati before the warm-up lap.
Irwin, who is 18 points ahead of Bridewell, said: “It’s another podium which is always good but after winning I felt I could earn another one today.
“The edge grip was a bit problematic and the track was a bit wet, especially in the last corner.
“I felt comfortable when I got back on Pete halfway through, but then Andrew passed me, and I finished third and then fourth. But I had to fight really hard for that.
OMG Yamaha’s Bradley Ray was crowned champion after finishing fifth in Saturday’s race but crashed out in race two on lap two at Paddock Hill Bend.