The home side - who came into the contest in second place and 5.5 points behind leaders Yorkshire - brought their second innings to an end in the morning session following the removal of Phil Mustard (73) and Usman Arshad (34) by declaring on 268 for eight, setting their opponents a victory target of 402.
Third-placed Sussex then made a poor start as Luke Wells was dismissed by Graham Onions - his fifth wicket of the match - having put only four runs on the board.
Mitchell Claydon later made Michael Yardy (25) his fourth victim of the game and at the interval Sussex were on 60 for two, requiring 342.
Fourth-placed Middlesex were firmly in control of their encounter with second-bottom Surrey at the Kia Oval, declaring on 235 for nine in their second innings to leave their hosts needing 385 to win.
Surrey, who had managed only 145 in their first innings after being tormented by Ollie Rayner, who claimed eight wickets, progressed to 37 without loss at lunch.
In the relegation battle between third-bottom Somerset and basement boys Derbyshire at Taunton, the former were making good progress in their second innings, going in at the break on 368 for seven - a lead of 173.
Nick Compton contributed 95 before falling to Antonio Palladino.
Meanwhile, at Trent Bridge champions Warwickshire's second innings was at 126 for four, putting them 65 in front of Nottinghamshire.