The Hungarian swimming star, affectionately known as the "Iron Lady" surged to victory in the 100m butterfly to cap a superb campaign at the championships in Windsor, Ontario.
Hosszu touched the wall 55.12sec, taking gold ahead of Kelsi Worrell of the United States (55.22) and Japan's Rikako Ikee 55.64.
The 27-year-old Hosszu had already stamped her class on the championships with wins in the 100m, 200m and 400m medley as well as the 200m butterfly and 100m and 200m backstrokes.
Sunday's final win at the WFCU Centre completes a phenomenal 2016 for Hosszu, who also lit up the Rio de Janeiro Olympics with three gold medals.
There was more gold too on Sunday for South Korea's Park Tae-Hwan, who added the 1,500m title to the 200m and 400m crowns won earlier in the week.
The win ensured Park finishes the year on a triumphant note after a tumultuous season which saw him battle to compete in Rio after serving a drugs ban only to come away from Brazil empty-handed.
Park finished well clear of his rivals in 14:15.51, ahead of Italy's Gregorio Paltrinieri, who clocked 14:21.94 for silver and Poland's Wojciech Wojdak, who took bronze in 14:25.37.
Elsewhere Sunday, South Africa's 2012 Olympics breaststroke champion, Cameron van der Burgh, won gold in the 50m discipline.
Van der Burgh took the title in 25.64sec, finishing ahead of Peter Stevens of Slovenia (25.85) and Brazil's Felipe Lima (25.98).
But there was more disappointment for US teenager Lilly King. King, one of the rising stars of US swimming who won gold in the 100m breaststroke at the Rio Olympics, finished outside the medals in the 200m breaststroke.
King, pipped for gold in the 100m breaststroke on Saturday, finished fourth in a race won by Britain's Molly Renshaw, who clocked 2:18.51.
Canada's Lauren Wog took silver in 2:18.52 while another Briton, Chole Tutton, won bronze with a time of 2:18.83.
Triple Olympic champion Ranomi Kromowidjojo meanwhile won gold in the 50m freestyle.
The Dutch sprinter, who winner of Olympic gold in the 4x100m freestyle relay in the 2008 Games before a 50m/100m double in London four years later, took first in 23.60sec.
Italy's Silvia Di Pietro won silver in 23.90 with Madison Kennedy of the United States bronze in 23.93.