Just as he had in Wales’s opening 2-1 win over Slovakia, Gareth Bale put Chris Coleman’s side ahead with a long-range free-kick that England goalkeeper Joe Hart could only fumble into the net.
But Vardy and Sturridge came on at half-time and after the former had equalised in the 56th minute, the latter smuggled in a stoppage-time winner that fired Roy Hodgson’s men to the top of the group.
Wales are a point back in second place, above Slovakia on head-to-head record, and need to beat Russia in Toulouse on Monday to guarantee one of the two automatic qualifying berths.
A draw against Slovakia in Saint-Etienne will suffice for England and they will approach the game with renewed optimism after belatedly kicking their tournament into gear.
It was the 102nd meeting between the teams, but the first at a major championship, and the boxy, British-style Stade Bollaert-Delelis provided an ideal setting on a day when fears of fan violence failed to materialise.
Wayne Rooney’s foul on Robson-Kanu gave Wales a free-kick 35 yards out in a central position. Though Bale’s shot had vicious pace and dip, Hart should have done better than palm it inside his left-hand post.
Despite the charge it seemed Wales would hold out, only for Sturridge to steer a shot past Hennessey in the stoppage time, silencing the Welsh hordes.