Needing 448 to avoid the follow on, Warwickshire will resume on the third morning on 88 for two, their decision to bowl first on a benign pitch having spectacularly backfired.
After Ricardo Vasconcelos and Will Young scored centuries on the first day, Luke Procter added another, a painstaking unbeaten 100 from 199 balls in four and a half hours.
Supported by Josh Cobb (66 from 95 balls), the in-form former Lancashire player lifted the visitors to an imposing total against an injury-hit attack manfully led by Australian import Nathan McAndrew (three for 121).
After 154.1 overs in the field, Warwickshire then lost Alex Davies and Rob Yates in the first 20 overs.
They will look to England man Dom Sibley (37 not out, 120) balls to lead the required massive rearguard action.
After resuming on the second morning on 372 for two, Northamptonshire quickly lost Emilio Gay, bowled by McAndrew for 45 (117 balls).
Rob Keogh batted positively for 27 (28 balls) but was then bowled through the gate by McAndrew who managed to prise some life from the batsman-friendly track.
Procter plodded through the morning session for 20 runs but Cobb, given a rare chance in red ball cricket, showed more enterprise.
He struck four fours and three sixes and his fifth first class century was beckoning when he responded to a dodgy call for a single from his partner and was beaten by Davies' direct hit from cover.
Davies then accepted a catch on the square leg boundary to remove Lewis McManus and end Danny Briggs' long wait for a wicket.
Procter and Matthew Kelly added an unbroken 62 in 10 overs before the declaration arrived when Procter ladled Yates over the long leg rope to reach his sixth first class century.
Northamptonshire's 17th-biggest first class total, albeit slowly accumulated at times, put their hosts under scoreboard pressure and their bowlers struck twice early on.
Davies sped to 29 (three fours and a six) but fell lbw to Jack White, in his first Championship appearance of the season, and Yates edged Kelly to Young at second slip.
At 57 for two the champions were facing a mountainous escape mission.
Sibley and Sam Hain avoided further mishaps in the last 18 overs of the day but much of that mountain remains ahead of the Bears.