He originally planned to retire after the Summer Olympics in Rio De Janeiro the previous year, but decided to return due to his love for the London crowds.
Meanwhile, young American Christian Coleman burst onto the athletics scene as the new favorite to dethrone Bolt, clocking a world-leading 9.82 seconds at the NCAA Championships and going on to win the 100-200 double.
His only defeat came at the US Championships, where fellow Tennessee Vol and 2004 Olympic champion Justin Gatlin overtook the inexperienced Coleman, who overstrided towards the finish.
Meanwhile, Bolt's training partner and 2011 World Champion Yohan Blake, continued his injury comeback by winning the Jamaican 100m title in 9.90, the second fastest time of the year.
CJ Ujah of Great Britain appeared to be in top form, winning 3 Diamond League races in Rome, London, and Rabat, the latter in 9.98 seconds.
Other key players included co-European record holder and 3-time global finalist Jimmy Vicaut of France, 7th-ranked Thando Roto of South Africa, and Rio finalist Ben Youssef Meite of the Ivory Coast Just days before the championships, De Grasse pulled out with a hamstring injury and was forced to miss his final chance to defeat Bolt.
Japanese runner Abdul Hakim Sani Brown placed himself as a favorite and surprised many by beating Blake in the second heat.
In the second semi-final, Yohan Blake barely held off the hometown favorite Reece Prescod, who had a sudden surge of speed in the last ten metres to take the automatic qualifying spot from Su Bingtian of China.
Coleman continued with his usual fast start, with Bolt next to him lumbering behind by a metre in fourth expecting to make up ground on Jimmy Vicaut of France and Su Bingtian inside him.