With the runner-up finish, Dixon unofficially reclaimed the championship lead after seven of 17 races with 275 points.
Reigning champion Simon Pagenaud will line-up only P7 for Race 1, after a frustrating qualifying session for the Penske racer.
The victory was Graham Rahal's first of the season and made him the seventh IndyCar driver to reach Victory Lane this season. "Physically for me, it was tougher than normal", said Dixon. Hinchcliffe finished third, completing a Honda sweep of the top three finishing positions. Indy 500 victor Takuma Sato was also undone by strategy, finishing eighth, while recent Indy Lights champions Ed Jones and Spencer Pigot rounded out the top 10.
Americans Josef Newgarden and Alexander Rossi rounded out the top-five at fourth and fifth respectively.
Scott Dixon finished a remarkable second in the opening race around the streets of Belle Isle on Saturday despite racing with a painful left ankle, which he has been struggling with throughout the week following his vicious crash during the Indianapolis 500. Sunday's IndyCar schedule will follow a similar path here at the Belle Isle circuit.
For Dixon, he will now be resting the ankle and preparing himself for more of the same on Sunday for race two, although he hopes to improve the performance of his auto to be in with a better shot of victory. "But she seems to be OK".
Helio Castroneves, who shared the front row with Rahal after his pole run was erased by IndyCar officials for not slowing enough under caution during qualifying, led 11 laps but abandoned a two-stop strategy and faded to seventh at the finish.
"I'm over the frustration already", he said. "It's hard. Obviously when you have it, you don't want to miss opportunities, but hopefully the weather holds up and we can do it again".
Rahal ultimately crossed the line six seconds clear of the field to become IndyCar's seventh different victor in the opening seven races of the season, as well as coming good on his pre-race promise that he could dominate. Following that race, the series will shift to Texas Motor Speedway for a race under the lights on June 10.