Riders will leave Woodman Point about 6am on February 6 ahead of a 50km round trip to Rottnest Island.
Organiser Fran Boyce said the event was a great way to remember her grandma Beryl Black, who died from motor neurone disease.
She also wants to raise $10,000 for the Motor Neurone Disease Association of WA.
“She loved the beach and she rode with us all the time,” Ms Boyce said.
“We often had a day out at the beach with a picnic and she enjoyed having a ski.”
Ms Boyce said planning for the crossing began two years ago.
She had hoped Ms Black would be around to see it run.
“Sadly we didn’t get it organised in time but I think she would be proud of what we have achieved with this event,” she said.
Jet skis are not usually allowed more than five nautical miles from shore, but the Department of Transport granted special permission to allow the crossing.
Waterways safety management director Chris Mather said the exemption was given with a number of safety conditions.
Ms Boyce said the fact it was a rare opportunity made it extra exciting.
“It’s exciting because you aren’t allowed to cross the channel on a jet ski normally and we think it’s a brilliant way for people to challenge themselves,” she said.
“We think everybody is going to enjoy being a part of a big group of amazing adventurers all hoping to raise awareness for Motor Neurone Disease.”