The 26-year-old has 4,138 points after the opening four events of the competition at the Khalifa International Stadium.
She holds a 96-point advantage over Olympic and defending champion Nafi Thiam in Doha.
Johnson-Thompson, who came second to Thiam at last year's European Championships, excelled ahead of Thursday's long jump, javelin and 800m.
She posted two personal bests in the 100m hurdles and shot put.
The World Indoor pentathlon champion made the perfect start to kick-start her bid for gold with a huge lifetime best of 13.09 seconds in the 100m hurdles.
Johnson-Thompson appeared shocked by the time after winning her heat.
Her and Belgium's Thiam then went blow for blow in the high jump, both finishing with clearances of 1.95m.
In the shot put, one of Johnson-Thompson weaker events, she shone again to throw a personal best of 13.86m, to come second behind Thiam, who threw 15.22m.
In the 200m she clocked 23.08secs, a season's best, to win heat three.