Mark Davies put the brakes on Surrey at Hove after producing his best bowling display for Sussex.
The spinner took 6-83, but his side are still likely to face a difficult task to beat the division one leaders.
The visitors go into the third day leading by 251 runs having reached 261-8 in their second innings with half centuries from Ian Ward and Mark Ramprakash.
A score of over 250 batting last will present a stern test for Sussex against a team bidding for their third title in the last four years.
The pitch, damp early on due to midweek rain, now seems easier to bat on although Surrey subsided after tea as off-spinner Davies, who had previously not taken more than three wickets this season, took up the challenge from the Cromwell Road end.
The left-handed Ward and Jonathan Batty got Surrey away to a perfect start by sharing an opening stand of 121 in 33 overs.
Ward passed 1,000 runs in the Championship on the way to completing his 50 out of 82 with seven crisply hit fours off 69 balls.
Batty was only four short of his half century when he pushed forward to Davies and popped up a straight forward catch to substitute Carl Hopkinson at silly point.
Hopkinson was called up with skipper Chris Adams forced to rest a jarred knee.
Surrey were strongly placed at 140-1 at tea with Ward on 75, but Davies then got going to snap up five more victims to lead a Sussex fightback.
Ward's 127-ball vigil ended as he edged a catch to wicket keeper Matthew Prior shaping to cut Davies, and then James Kirtley ripped out Nadeem Shahid's off stump as he played down the wrong line.
Alistair Brown and skipper Adam Hollioake were removed in the same over from Davies, both being bowled attempting to cut, and Surrey were reduced to 190-6 when Rikki Clarke chopped a delivery from the spinner onto his stumps.
Ramprakash displayed great concentration in compiling a solid half century to pass 1,000 runs in first class cricket, and he and Alex Tudor had added 50 for the seventh wicket before both batsmen fell just before the close.
Kevin Innes broke the stand by having Ramprakash, who had struck five fours and a six in only his second Championship 50 at Hove, stumped by Prior and then in the next over Tudor was bowled leg stump by Davies.
All rounder Innes earlier struck a valuable unbeaten 41 to help give Sussex a slender first innings lead of 10 after they resumed on 139-7.
Innes extended his eighth wicket stand with Davies (30) to 46 before Billy Taylor joined him in a last wicket partnership of 31.
Taylor had showed gritty determination in facing 53 balls when he was caught at the wicket off Tim Murtagh leaving Innes undefeated in two hours and 20 minutes at the crease.
England fast bowler Tudor struck two early blows for Surrey by removing Davies and Kirtley to record his first five wicket haul this season.
Tudor faced Sussex having been released from the England squad ahead of the second Test at Trent Bridge, and Surrey's cricket manager Keith Medlycott reckoned on this performance he "looked like a million dollars".
Coming in off a slightly shortened run up following a shin injury, Tudor had Davies caught at first slip by Brown before Kirtley went the same way to a diving effort from skipper Hollioak.
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