Semenya is currently in London competing at the IAAF World Championship and will compete in 800m final on Sunday at 21:10 South African time.
Hopkins' first salvo was an article in the Mail Online on Friday, where she wrote that "back in January, Caster even married her girlfriend in a traditional wedding ceremony, appearing in the guise of a man.
"Yet, curiously enough, out here on the track, Semenya identifies as a woman."
Hopkins made similar comments on social media and posted images of Semenya marrying her wife Violet Raseboya, ending her tweet: "Seriously @IAAFWorldChamps?"
On social media South Africans reacted with outrage.
"Everyone please report Katie Hopkins to Twitter for offensive comments against our Caster Semenya. Let's #BellPottinger her," wrote Maggs Naidu.
"What nonsense is this Katie Hopkins person smoking kanti? Why is she bullying our very own Caster?" tweeted user BeingBonang.
"I am battling to understand the point in this tweet. You're a PR machine for hate!" tweeted Algoa FM radio presenter Wayne Hart.
Hopkins seemed to relish being the subject of attacks by angry South Africans, and even re-posted images of tweets calling for her to be banned from Twitter.
Other South Africans tweeted that Hopkins thrives on attention, and it would be better to just ignore her views.
Earlier this year Hopkins parted ways with her radio station LBC, after she called for a "final solution" in the wake of the Manchester Arena terrorist attack.
Hopkins was at the time widely criticised for using Nazi-inspired language. Source:News24