Flanker Justin Tipuric scored two tries as the Ospreys out-muscled Newport Gwent Dragons at the Liberty Stadium.
A penalty try and a touchdown for Scott Baldwin earned the Ospreys a bonus point, with Dan Biggar contributing 17 points with the boot.
Tom Prydie and Francisco Chaparro crossed for the Dragons with Kris Burton converting and dropping a goal.
But there was concern for Wales after Dragons number eight Toby Faletau was carried off with a neck injury.
Faletau was injured as he tackled Ospreys wing Eli Walker early in the second half.
There was a 10-minute delay as medical staff attended to the Lions back row forward, and he was carried off on a stretcher with his neck and back braced before being taken to Swansea's Morriston Hospital for assessment.
The Ospreys already had the game under control before the incident, with open-side Tipuric delivering a virtuoso performance.
But there was little hangover from those performances as the Ospreys pack dominated.
The Dragons had made a flying start, crossing for a try in the first three minutes courtesy of some good play and a slice of luck.
Skipper Andrew Coombs benefitting from a ricochet off the heel of Tom Habberfield before feeding Prydie, who scored wide on the right hand side. Burton converted.
The home team recovered from the early set-back with their pack taking control before Biggar's first penalty got them on the scoreboard.
Biggar was playing at full-back in place of the injured Richard Fussell, with Matthew Morgan filling in at fly-half.
Morgan made his presence felt as he sprinted 50 yards past a splintered Dragons defence, off-loading to Tipuric - who juggled the ball before crossing between the posts.
Biggar converted and added two penalties before the interval, though the Ospreys' lack of control at key moments meant the six-point half-time lead was scant reward for their dominance after Burton had dropped a goal.
A 10-point burst at the start of the second half put the game beyond the Dragons.
Morgan dropped a goal and then Tipuric was put clear from a lineout by Habberfield and chipped the ball over full-back Dan Evans before gathering and sprinting in for a superb individual try, which Biggar converted.
The injury to Faletau and a yellow card for replacement Ieuan Jones further disrupted the Dragons, whose seven-man scrum was shunted backwards before Lewis Evans infringed to concede a penalty try, with Biggar adding the conversion.
Scott Baldwin delivered the bonus point when he sneaked over from a rolling maul, and Chaparro's late try was a consolation for the Dragons, who were comprehensively out-played.
Ospreys: Daniel Biggar; Jeff Hassler, Jonathan Spratt, Andrew Bishop, Eli Walker; Matthew Morgan, Tom Habberfield; Ryan Bevington, Richard Hibbard, Aaron Jarvis, Alun Wyn Jones (capt), James King, Tyler Ardron, Morgan Allen, Justin Tipuric.
Replacements: Scott Baldwin, Duncan Jones, Adam Jones, Lloyd Peers, Joe Bearman, Tito Tebaldi, Ben John, Sam Lewis.
Dragons: Dan Evans; Tom Prydie, Ross Wardle, Lewis Robling, Hallam Amos; Kris Burton, Richie Rees; Owen Evans, Sam Parry, Dan Way, Matthew Screech, Andrew Coombs (c), Jevon Groves, Lewis Evans, Toby Faletau Lewis Evans.
Replacements: Hugh Gustafson, Nathan Williams, Francisco Chaparro, Adam Jones, Ieuan Jones, Jonathan Evans, Will Harries, Adam Hughes.
Referee: Nigel Owens
Assistant Referees: Neil Hennessy, Jon Mason (both WRU)
Citing Commissioner: Dennis Jones (WRU)
TMO: Tim Hayes (WRU)