Cox, who won a bronze medal in the women’s T38 100m on Friday, won the C4-5 time trial in the velodrome on Saturday. Dame Sarah Storey finished fourth.
Isabel Barr was the last British Paralympian to medal in two sports at the same Games, taking medals in both shooting and athletics at Seoul 1988.
Cox, who had a stroke aged 23, completed the 500m race in 34.598 seconds to take the lead in impressive style. Storey, a pursuiter rather than a sprinter, clocked a time of 37.068 seconds to finish just outside the medals.
Success for ParalympicsGB also came from the Olympic Stadium as Hannah Cockcroft retained her T34 100m title, and 15-year-old Kare Adenegan took silver in the same race.
Adenegan, 15, is the youngest athlete in the British squad and is the only racer to have beaten Cockcroft during the past four years in the T34 category.
Despite the pair being almost level at 40metres, Cockcroft powered ahead to finish in 17.42 seconds, setting a new Paralympic record.
Adenegan set a personal best of 18.29 seconds, and is one of a number of athletes inspired to take up sport after London 2012.
Tony Gold and Andy Small both medalled in the men’s T33 100m, taking silver and bronze respectively, with Daniel Bramall finishing in fourth place on his Paralympic debut.
Sabrina Fortune earned a first medal for Wales, claiming a bronze in the women’s F20 shot put with a personal best throw of 12.94m. Fortune, who has been progressing well throughout the season, was delighted.
Richard Whitehead, a crowd-favourite from London 2012, set a Paralympic record of 23.07 seconds, qualifying for Sunday’s T42 200m final.
Graeme “bullet” Ballard suffered disappointment in the T36 100m final, with Mohamad Ridzuan Mohamad of Malaysia taking the gold medal with a time of 12.07 seconds. Ballard did not have the strong start he is renowned for, finishing in fifth place.
Alice Tai impressed in the women’s S10 100m backstroke, winning a bronze medal, just four years after she was a flag bearer in London 2012.
Tai, who was born with a club foot, clocked a time of one minute 9.39 seconds. New Zealand’s Sophie Pascoe won gold.
Sascha Kindred returned to the pool as a veteran of Paralympic sport but could only manage sixth in the men’ S5 50m freestyle, while Andrew Mullen finished just outside the medals in fourth in the men’s S5 50m butterfly.
The first gold of day three came from Britain’s Andy Lewis, winning the PT2 Para-triathlon on its first ever running at a Paralympic Games.
The 33-year-old right leg amputee, finished in one hour 11 minute 49 seconds, and in an emotional post-race interview said “It brings tears to my eyes that I’ll be able to tell my kids that I won this gold medal” said Lewis.