A 26-21 victory over the third-placed Irish side, coupled with Munster’s surprise defeat to Edinburgh, puts Scott Johnson’s men three points clear at the head of the standings.
Barry Davies and Hanno Dirksen scored first-half tries, while Dan Biggar followed up his 20-point haul against Ulster with a further 16 points courtesy of two conversions and four penalties.
The Ospreys led 17-10 at the break and, although the game remained tight throughout, last year’s beaten semi-finalists claimed a fifth straight win following previous successes against Leinster, Edinburgh, Treviso and Ulster.
Davies gave the three-times champions the perfect start when he crossed with the game just six minutes old, despite the visitors having dominated territory and possession in the opening stages.
Connacht captain Gavin Duffy’s converted score brought the sides level again but a first Biggar penalty and Dirksen’s 33rd-minute try stretched the advantage to 10 points.
Niall O’Connor reduced the deficit to a single score before the break but missed another effort shortly into the second half. A 54th-minute yellow card to Ospreys lock Ian Gough looked to have handed the initiative to the Irish outfit but another three-pointer from Biggar followed just two minutes later.
Connacht did cut the gap to just five points while Gough was in the sin bin thanks to Duffy’s second score and the Ospreys defence had to withstand some further heavy pressure in the final quarter.
The final 10 minutes saw a 73rd-minute penalty from Biggar followed by a drop goal from O’Connor two minutes later before Biggar extended the lead to eight with 78 minutes played.
O’Connor’s second penalty secured a losing bonus-point for Eric Elwood’s side but it was the Ospreys who left the Liberty Stadium with more to shout about as they continued their 100-per-cent start to the new season.