The Czech cruised to an error-free win in a world-lead, national record time of 52.83 seconds, with American duo Dalilah Muhammad (54.09) and 2011 champion Lashinda Demus (54.27) picking up silver and bronze.
Medal hope Shakes-Drayton - who impressed in qualifying but showed ragged technique at times - started poorly and was going backwards in the closing metres, finishing seventh in a poor time of 56.25.
"It was going all right until the first hurdle and after the first hurdle my knee just felt funny," she said.
"It was going so well, leading the heats and the semi. But tonight after the first bend I was just going back and back and back."
Her compatriot Eilidh Child was far more impressive, coming fifth, with her time of 54.86 only half a second shy of a medal.
It is the 26-year-old Hejnova's finest achievement to date, having picked up bronze at last year's London Olympics.
"To run under 53 seconds - it is fantastic. The reason for my improvement is that I changed coach and I now train with the boys," the 26-year-old Hejnova said.
"They are faster so they are my motivation."
After London 2012, Hejnova linked up with Dalibor Kupka, former coach to 2004 Olympic decathlon champion Roman Sebrle, and she counts European 400 metres gold medallist Pavel Maslak among her new training partners.
"It's a fantastic season for me. I'm still unbeatable... and I broke my personal best and the national record," Hejnova added.
It was only the second track gold for the Czech Republic at a world championships after Ludmila Formanova won the 800 in 1999.
While Shakes-Drayton and Demus were considered the favourites after Olympic champion Natalya Antyukh failed to reach the final, Hejnova had qualified fastest ahead of the aforementioned pair and - unlike them - improved on that time in a flawless final run.
The Czech's excellent technical hurdling ultimately saw her build up an unassailable lead in the middle part of the race as the fast-finishing Demus and Muhammad failed to get close in the final strait.
It is back to the drawing board for the highly-rated Shakes-Drayton, who often performs well in the season and qualifying but fails to make an impact on major championships.