British number one Shuker, 37, and France's Stephane Houdet, 46, defeated Alfie Hewett, another Briton, and USA's Dana Mathewson 6-3 7-5.
"It was really good fun," Shuker said. "Dana and Alfie played really well and Stephane is just a gentleman.
"He's always encouraging and if you make a mistake, there's no negativity. For me it was just total enjoyment."
Shuker, who won the mixed doubles with compatriot Andy Lapthorne in 2015, when the mixed doubles was last held at the British Open, added that she intended to complete a hat-trick of victories with Houdet next year.
In a match that featured high-quality rallies, it was top seeds Shuker and Houdet who got an early break of serve, winning the first two games.
A skilful volley from Shuker at the net secured the first set.
The second set was tighter but Houdet's powerful forehand and pinpoint accuracy, combined with Shuker's skill at the net, proved too much for Hewett and Mathewson.
At 5-5, it was the eventual champions who took control, taking the next two games to win the match.
The mixed doubles was popular with both the crowds and the players at this year's British Open.
However, not all tour events have a wheelchair mixed doubles tournament - there are none at any of the Grand Slams - and those involved do not currently receive ranking points.
"You get to play a match with someone you would never get to play with - I'd never get to play on the same court as Houdet in any other circumstance," Mathewson said.
"The style of play is different and I thought it was a really good way to mix things up."
All four of the British Open finalists said they wanted to see more mixed doubles events on tour.
"I would definitely encourage other tournaments to get the event going," Hewett said.
"I think if there was some sort of incentive or reward for playing as well, it would get more playing. It doesn't have to be money. It can be vouchers, like we got here, or something else."
Shuker added: "As a woman playing with a guy on the court, it's unbelievable to see what they're able to do. It's exciting. I think the more that it's in the tournaments, the more that people will start to play - and hopefully it will grow more and more."
Houdet said he thinks the event could well be successful on one of the world's biggest stages.
He said: "I really want to see the event at the Paralympics, definitely."
Earlier on Sunday it was also runners-up honours for Hewett in the men's singles, as he lost 6-4 6-3 to world number one Gustavo Fernandez.
It was always going to be tough for Hewett with Fernandez enjoying an incredible run of form catapulting him to the top of the rankings just before Wimbledon.
In the quads division, Andy Lapthorne lost his singles final to world number one David Wagner of the USA.
Lapthorne started well with two love service games - but fresh from his quads doubles victory yesterday, Wagner won eight games in a row to seal a 6-3 6-1 victory.
In the juniors section, there was double success for 15-year-old Ruiari Logan, who retained his singles title and took the British Open juniors mixed doubles title with Ellie Robinson as well.
Logan also competed in the senior draw this week, scoring his first senior men's singles victory before losing in round two to Hewett.
Lucy Shuker defended her mixed doubles title on the final day of the British Open in Nottingham.