Skelton, who was part of Britain's gold medal winning showjumping team at London 2012 last summer, comfortably triumphed in the Grandstand Welcome Stakes at the NEC.
The 55-year-old, riding grey stallion Zero, won the first international competition, a one-round speed class, in Birmingham by more than six seconds ahead of American Lauren Hough.
He clocked a time of 61.64 seconds with Hough posting 68.11 for second and fellow Brit Ellen Whitaker placing third after recording 69.90 aboard Lola V.
Skelton was joined in the field by Olympic gold medal winning teammate Ben Maher, who won the team title at this year's European Championships as well as individual silver.
However Maher had to make do with 19th in the Grandstand Welcome Stakes in Birmingham aboard Dusty but will be back in action at the NEC.