Batsman Gordon Muchall completed a match-changing century before Hampshire stuttered in their response on Day Two at the Ageas Bowl.
Muchall scored a measured 14th career First Class century before the Durham attack restricted the hosts to 119 for three at the close.
On a grim and grey day at the Ageas Bowl, Muchall continued where he left off the previous evening, frustrating Hampshire with his patient brand of cricket.
Muchall had rebuilt Durham’s innings on the opening day, with Michael Richardson, after they had slumped to 91 for four at lunch.
And the 32-year-old batsman went past his second ton of the season in 229 balls in a six hour marathon at the crease.
He and Usman Arshad strode past a third batting point on their way to a 128-run stand for the seventh wicket.
Arshad scored his first fifty since September 2013 – with a 92-ball effort before he edged Gareth Berg to James Vince at first slip for 60.
Centurion Gordon Muchall said: “I’ve been batting well in the last couple of weeks and not been able to get a score.
“I was disappointed with my shot in the second innings against Warwickshire so it was important for me to get a big score this week.
“It was nice to get a decent partnership with Michael and then push on to get 400 which is a couple above par on that wicket.
“Take a few early wickets tomorrow and we will be right in the box seat.
“Benny (Arshad) played brilliantly and he is quite an aggressive batsman so when he’s in his zone he scores quite freely.
“The wicket wasn’t a free scoring wicket, it is a little bit two paced and a bit of up and movement.
“It was important to get another partnership and put a good total on the board.
“We didn’t get maximum batting points but a big first innings in the game will set us up in the game, early wickets tomorrow and we are in the box seat.”
Australian John Hastings added some impetus by slapping Liam Dawson over the ropes for a maximum – but fell for 22 sweeping across the line to give leg spinner Mason Crane his maiden First Class wicket.
Dawson – who is celebrating a century of First Class matches – collected his 150th format wicket when he finally managed to find a way to see off Muchall, who departed for a match changing 145, before Graham Onions slogged to Jackson Bird – Durham bowled out for 421, their highest total of the season.
Chris Rushworth bagged his 56th County Championship wicket of the season as Hampshire’s reply started with a stutter as he pinned Jimmy Adams, who stepped down from captaincy this week to concentrate on his batting, in the seventh over as Durham got a perfect start.
Liam Dawson then mistimed a pull shot to Usman Arshad at mid-off off John Hastings after putting on 30 with Michael Carberry.
James Vince looked in good touch with a couple of trademarked cover drives but edged Ryan Pringle to Paul Collingwood at first slip as he looked set on 19.
Carberry, who returned to the top of the order after a stint at number three, scored his sixth half century of the season – although he is still yet to reach three figures – brought up in 93 balls.
The former England Test batsman sweetly timed a hook shot for a six to reach 57 when the rain stopped play just after 5pm, with Will Smith ably reaching 27.
Hampshire First Team coach Dale Benkenstein said: “We’re on the back foot, that was a huge score.
“The only good thing is that it did look a lot easier when the ball got older, with the new ball it was quite tough.
“We’re going to have to bat we but I’m really pleased with that last partnership which is something we haven’t seen in the past few games.”