Opiyo struck a sublime freekick in the 20th minute before a brilliant turn-and-shoot inside the box quarter of an hour later doubled the advantage for Simba wa Nairobi.
Elsewhere, Nzoia Sugar picked their first win of the season with a well-worked 3-1 victory over Kariobangi Sharks in Bungoma while at the Moi Sports Centre Kasarani, Kenya Police FC and Wazito played to a 1-1 draw.
Meanwhile, Kakamega Homeboyz maintained their place on top of the standings despite a barren draw at home against Bidco United.
At the Ruaraka Complex, City Stars bounced back from two winless matches to pick their fifth victory of the season.
They broke the deadlock in the 20th minute when Opiyo struck a sublime freekick, curling the ball beyond the wall and into the roof of the net after Ezekiel Odera had been fouled by Martin Ongori at the edge of the box.
City Stars had been the first to offer any attacking threat and were duly rewarded.
On the half hour mark, Opiyo almost completed a brace of freekicks from similar range, this time when Timothy Ouma was hacked down at the same distance.
However, his well taken effort, this time swung in opposite direction coming off the bar. Sven Yidah pounced on the rebound and scored, but was flagged down for offside.
Five minutes later though, there was no denying the experienced midfielder his double, and he sure made it even more sensational.
Opiyo picked up Nicholas Kipkurui’s pass inside the box, turning swiftly with some deft piece of skill before slamming the ball past a dazed Bryne Omondi in Mathare’s goal.
Ouma almost gave City Stars a 3-0 halftime lead when he did well to drift in from the left, but his shot flew straight to the keeper.
In the second half, Mathare came back from the breather with some hope of getting the two goals back and they pinned City Stars in their own half.
However, their biggest undoing was their poor decision making in the final third. They came closest five minutes to time but keeper Jacob Osano made a brilliant double save, first stopping from Danson Kago before denying Eugene Wethuli off the rebound.