The 25-year-old, the fastest Paralympian in the world, added the 200m - T13 crown to his 100m title with another dominant display.
And he went a step further than the self-confessed Jamaican 'living legend' Bolt, by smashing the world record for the third time in four races at the Olympic Stadium.
The only one in the final to have gone under 22 seconds, the Irish sprinter - who trains in Florida with USA star Tyson Gay - clocked 21.05. That was 0.90 ahead of Alexey Labzin of Russia and 0.38 quicker than Smyth's old world-best mark.
Another Russian, Artem Loginov, took bronze in a personal best of 22.03.
Victory ensured that the Irish athlete has successfully defended both T13 titles he won four years ago at Beijing 2008.
He said: 'The people here and the British and the Irish, the cheers and support for me has been absolutely fantastic and I'll never forget it.
'It is a home Games and it's been a pleasure to be here competing.'
Meanwhile, Oscar Pistorius showed he is in no mood to let his Paralympic 400m - T44 crown go the same way as his two other individual track titles.
The South African has this week lost his 100m and 200m titles but the 400m is the event in which he reached the Olympic semi-finals and, judging by the two heats tonight, he is looking strong for gold tomorrow.
The 25-year-old ran a strong first half of the race before he was able to ease up long before the line, coming home in 48.31.
The next fastest qualifier, Blake Leeper of the USA who won the first heat, was more than two seconds behind.
Brazil's 200m champion Alan Fonteles Cardoso Oliveira also made it through after blasting the first 300m and jogging over the line in 53.02.
Tatyana McFadden roared to her third Paralympic gold medal in the 1500m - T54 title to add to her 400m and 800m crowns.
The American hit the accelerator with half a lap to go to hold off the challenge of Switzerland's Edith Wolf and win in 3:36.42. Another USA racer, Shirley Reilly, took bronze.
The USA's Raymond Martin, 18, won his third track title with victory in the 800m - T52, finishing ahead of Japan's Tomoya Ito in silver and Mexican Leonardo de Jesus Perez Juarez in bronze.
It was a good evening for China, with Liu Ping winning the 100m -T35, Li Huzhao the 200m - T53, Zhang Lixin the 400m - T54 and Wang Yanzhang the Discus Throw - F32/33/34.
Australia's Todd Hodgetts won the Shot Put - F20, while Iran's Javad Hardani claimed the Discus Throw - F37/38 title.
South African Ilse Hayes won the Long Jump - F13, Chile's Cristian Valenzuela the 5000m - T11 and Germany's Heinrich Popow clinched gold in the 100m - T42.
Jose Sayovo Armando won the 400m - T11 to earn Angola's first gold at the Olympic Stadium.