The Briton is the defending champion in the event and had been the world record holder until June when USA star Victoria Arlen set a new mark.
Simmonds was beaming after setting a time of 5:24.64, a Paralympic and European record and personal best, just 0.18 outside Arlen's world mark.
She said: 'Really pleased. I am shocked by it. All my coach (Billy Pye) said leading into it was to go in there and hopefully do a 5:30.
'But, yeah, really happy - I've just done a PB in a heat swim which gets me ready for tonight. It's going to be very tough but a very exciting race but I am looking forward to it.'
It's going to be very tough but a very exciting race but I am looking forward to itEllie Simmonds
Arlen clocked a winning time of 5:25.19 in the second heat and received a boost soon after when the International Paralympic Committee (IPC) confirmed that after a review she will continue to compete in the S6 class.
Mallory Weggemann of the USA came to the pool today to qualify seventh for the 100m Breaststroke - SB7 final.
She said: 'I am just happy to make the top eight right now. This is my first race at my first Games. I had some nerves to shake out but I am excited to come back tonight and just race.'
Sophie Pascoe continued her stunning start to the Games with another world record, this time in the 100m Butterfly - S10. She swam 1:04.97, taking 0.69 off her own mark from April.
China's Yang Bozun also set a new world mark in the men's 50m Freestyle - S11 of 25.33, with Cecilia Camellini lowering Italian countrywoman Maria Poiani Panigati's record to 31.15 in the women's equivalent.