The USA athlete won the one-length dash in 31.13, a new Paralympic and American record, to claim the title in style ahead of Maddison Elliott of Australia and Jiang Shengnan of China.
Weggemann said: 'Oh my God, it feels absolutely amazing.
'I've been dreaming of being on that podium and hearing the anthem for four-and-a-half years. I didn't expect it but I wanted it.
'It was a tough competition, I knew I had a tough race but I gave it my all and that was enough tonight.'
Weggeman's achievement was one of the standout performances on another superb night of Swimming action.
Rudy Garcia-Tolson swapped from Athletics yesterday where he came ninth in the 100m - T42 to set a world record in the heats of the 200m Individual Medley - SM7.
However, the USA athlete could not repeat his feat this evening when Ukrainian Yevheniy Bohodayko not only wrested his title but also his world record in 2:33.13.
In the women's equivalent, Australia's Jacqueline Freney also set a world mark of 2:54.52.
Jon Margeir Sverrisson also set a new world record of 1:59.62 in a thrilling 200m Freestyle - S14 meaning that there were three world records for the Aquatics Centre crowd to enjoy in as many races.
Ihar Boki lowered his own 100m Freestyle - S13 mark to 51.91 while Leslie Cameron took almost five seconds off his 150m Individual Medley - SM4 record.
Elsewhere, Great Britain's Jessica-Jane Applegate was roared home to a sensational victory in the women's 200m Freestyle - S14, Dmytro Zalevskyy won the men's 100m Backstroke - S11 and Japanese Rina Akiyama claimed the women's 100m Backstroke - S11 title.
USA star Kelley Becherer won the women's 100m Freestyle - S13, Roman Makarov did likewise in the men's 100m Butterfly - S12, Du Jianping triumphed in the men's 150m Individual Medley - SM3, Joanna Mendak of Poland won the women's 100m Butterfly - S12 and Australia stormed to victory in the men's 4 x 100m Freestyle Relay - 34 points.