The visitors dominated the game until the 37th minute when Cisse pounced to hit his 11th goal of the season totally against the run of play.
Christian Benteke and Scott Sinclair had earlier produced excellent saves from Tim Krul and Villa twice had goals ruled out for offside before Ayoze Perez hit the post with a header.
But Villa could not trouble the scorers for the sixth away game in a row and remain in 19th place in the Premier League table, while John Carver’s men picked up their first home victory of 2015.
Newcastle were buoyed before kick-off with the news Jonas Gutierrez was fit to return to the squad after a 17-month absence following his successful battle against testicular cancer.
However, it was Sherwood’s changes – Ron Vlaar, Kieran Richardson, Carlos Sanchez and Carles Gil making way for Jores Okore, Matthew Lowton, Ashley Westwood and Tom Cleverley – that made the desired impact, with the visitors making a promising start at St James’ Park.
Benteke was at the heart of Villa’s early dominance, firing a dangerous cross into the heart of the Newcastle six-yard box but Gabriel Agbonlahor could not make contact with the goal at his mercy. Minutes later, Agbonlahor was in the thick of the action again as he had the ball in the back of the net net but he was correctly adjudged to be offside after making his run too early.
A Benteke volley hit the side netting before the Belgian striker’s athletic bicycle kick produced a superb save from Krul, but all Villa’s excellent work was undone just after the half-hour mark as Okore missed Daryl Janmaat’s cross and Cisse was on hand to fire the ball past Guzan against the run of play.
Newcastle came out after the break in a more positive mood but continued to struggle with their final ball, with Gabriel Obertan wasting a beautiful 49th-minute pass from Sammy Ameobi by shooting wide from an impossible angle.
Cisse might have doubled his tally with 58 minutes gone when he got his head to an Ameobi free-kick, but he steered his effort wide of the post.
The Magpies were dealt a blow when Massadio Haidara, one of only four fit senior defenders, was carried from the field on a stretcher and replaced by Ryan Taylor, and their mood might have darkened further had Krul not managed to block Tom Cleverley’s 62nd-minute shot with his legs.
But the Holland international very nearly gifted Villa a 71st-minute equaliser when he failed to collect Westwood’s corner, sparking a goalmouth melee which ultimately ended with Benteke putting the ball into the net from Westwood’s cross, but from an offside position.
Substitute Perez was denied a second goal by the post after Brad Guzan had managed to get only his fingertips to Ameobi’s 76th-minute corner, but one proved to be enough to hand Sherwood his second successive defeat as Villa boss.
Newcastle: Krul (7), Janmaat (7), Coloccini (7), Williamson (6), Haidara (6), Obertan (6), Sissoko (7), Abeid (6), Ameobi (7), Riviere (7), Cisse (8).
Subs used: R.Taylor (6), Gouffran (5), Perez (6).
Aston Villa: Guzan (6), Hutton (6), Okore (5), Clark (6), Lowton (6), Sinclair (6), Delph (7), Cleverley (6), Westwood (7), Agbonlahor (7), Benteke (7).
Subs used: Bacuna (5), Weimann (6), N’Zogbia (5).
Man of the Match: Papiss Cisse