Hampshire let Durham off the hook before fighting back late on day one at the Ageas Bowl.
The hosts are desperately in need of a victory to boost their chances of avoiding relegation from the top flight of the County Championship.
But after reducing the visitors to 14 for two and 91 for four, Hampshire were unable to press home their advantage.
Only two Jackson Bird wickets late in the day saw the game back in the balance at 278 for six heading into day two.
James Tomlinson’s return to the first team coincided with an impressive start for the hosts – after skipper James Vince, who has taken the reins from Jimmy Adams, lost the toss.
The left-arm seamer, who had been left out of Hampshire’s previous two first-class fixtures, removed Graham Clark and Paul Collingwood during a fruitful morning session.
Bird (three for 80) had Mark Stoneman trapped leg before wicket in the first over.
And Liam Dawson, who was recalled from his loan spell at Essex for the match, then dropped Scott Borthwick at second slip off the very next ball.
The Hampshire all-rounder had shelled the Durham man again before Tomlinson took over to strike his first blow.
First-class debutant Clark was struck in front by the pace bowler and the umpire obliged, raising his finger to send the batsman packing for just eight.
Tomlinson (two for 47) then accounted for Paul Collingwood – the England all-rounder also making eight before chipping a drive to Adams, who has handed over the captaincy to concentrate on his own batting.
Borthwick finally departed to the final delivery of the morning – leg before wicket to Dawson for 49 – as he attempted to sweep.
But when Durham resumed on 91 for four after lunch, Hampshire were unable to make the most of their advantage.
Wicketkeeper-batsman Michael Richardson (91) and Gordon Muchall (85 not out) steered the visitors out of trouble with a partnership of 142 for the fifth wicket.
Hampshire leg-spinner Mason Crane impressed on debut but he was unable to find the breakthrough.
That was left to Bird, who struck with two wickets in two balls to keep the home side in the game.
He had Richardson trapped leg before wicket and then Ryan Pringle snaffled by Vince with his next delivery to set up an intriguing second day.