In perfect seam bowling conditions, 16 wickets fell with Keith Barker taking a career-best 7-46 as the visitors were dismissed for 155 in response to Hampshire' s first innings score of 226.
But Dane Paterson inspired a Nottinghamshire fightback, reducing the hosts to 133-7 at the close after James Vince and Liam Dawson had bolstered the hosts' advantage with an 82-run stand having come together at 28-4.
It leaves a fascinating match firmly in the balance although heavy rain is expected to disrupt much of day three.
Resuming on 29-1, Nottinghamshire were stopped in their tracks by a stunning burst from Barker that saw the table-toppers slump to 31-4 inside the first 15 balls.
The veteran left-armer dismissed Ben Duckett with the first delivery of the morning and struck again with the fifth when Joe Clarke chipped the former Warwickshire man to Brad Wheal at mid-wicket.
Nottinghamshire skipper Steven Mullaney came and went for just two to become Barker's fourth victim before Tom Moores was pinned on the crease and thumped on the pad to hand the 34-year his 17th First Class five-wicket haul.
Opener Ben Slater batted well amidst the rubble of his side's top order, posting a gritty half-century in a 70-run stand with Liam Patterson-White.
But Slater departed shortly after lunch when he mistimed an attempt to withdraw his bat and the ball kissed the edge and found its way into the gloves of Tom Alsop to hand Barker his sixth wicket with Joey Evison becoming his seventh to leave Notts in desperate trouble at 115-7.
Patterson-White brought up his 50 in a stand of 30 with Brett Hutton but the duo departed in successive balls with Brad Wheal bowling Patterson-White for 53 and Hutton caught in the deep by Felix Organ off James Fuller for 13.
Wheal wrapped up the innings by dismissing Paterson for six to deliver Hampshire a handy 71-run lead.
Openers Ian Holland and Joe Weatherley got off to a solid start putting on 26 for the first wicket, only for Paterson to rip through the top order.
Holland was the first to depart for 16 with Tom Alsop soon following him back to the pavilion after a second-ball duck before Joe Weatherley feathered a catch to Tom Moores off Luke Fletcher.
Matters were compounded for the hosts when Nick Gubbins became Paterson's third victim to leave Hampshire struggling at 28-4.
Vince and Dawson steadied the ship but their crucial partnership was ended by Patterson-White who trapped Dawson lbw for 28 with Vince then having his off-stump uprooted by Fletcher for 52.
Patterson-White struck again four overs from the close when Felix Organ was lbw for 11 with Barker and Wheal unbeaten on 11 and one.